PA2H1_BOTAT
ID PA2H1_BOTAT Reviewed; 138 AA.
AC Q6JK69;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 62.
DE RecName: Full=Phospholipase A2 homolog 1;
DE Short=svPLA2 homolog;
DE AltName: Full=Myotoxin I;
DE Flags: Precursor;
OS Bothrops atrox (Barba amarilla) (Fer-de-lance).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=8725;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 17-56, FUNCTION, SUBUNIT,
RP TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=15225567; DOI=10.1016/j.toxicon.2004.04.013;
RA Nunez V., Arce V., Gutierrez J.M., Lomonte B.;
RT "Structural and functional characterization of myotoxin I, a Lys49
RT phospholipase A2 homologue from the venom of the snake Bothrops atrox.";
RL Toxicon 44:91-101(2004).
CC -!- FUNCTION: Snake venom phospholipase A2 homolog that lacks enzymatic and
CC anticoagulant activities (PubMed:15225567). In mice, it induces
CC conspicuous local myonecrosis, edema, and a systemic interleukin-6
CC response (PubMed:15225567). In vitro, it is cytolytic upon myoblasts,
CC and weakly bactericidal (PubMed:15225567). A model of myotoxic
CC mechanism has been proposed: an apo Lys49-PLA2 is activated by the
CC entrance of a hydrophobic molecule (e.g. fatty acid) at the hydrophobic
CC channel of the protein leading to a reorientation of a monomer (By
CC similarity). This reorientation causes a transition between 'inactive'
CC to 'active' states, causing alignment of C-terminal and membrane-
CC docking sites (MDoS) side-by-side and putting the membrane-disruption
CC sites (MDiS) in the same plane, exposed to solvent and in a symmetric
CC position for both monomers (By similarity). The MDoS region stabilizes
CC the toxin on membrane by the interaction of charged residues with
CC phospholipid head groups (By similarity). Subsequently, the MDiS region
CC destabilizes the membrane with penetration of hydrophobic residues (By
CC similarity). This insertion causes a disorganization of the membrane,
CC allowing an uncontrolled influx of ions (i.e. calcium and sodium), and
CC eventually triggering irreversible intracellular alterations and cell
CC death (By similarity). {ECO:0000250|UniProtKB:I6L8L6,
CC ECO:0000269|PubMed:15225567}.
CC -!- SUBUNIT: Homodimer; non-covalently linked (probable alternative/compact
CC dimer conformation in solution). {ECO:0000250|UniProtKB:I6L8L6,
CC ECO:0000269|PubMed:15225567}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15225567}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:15225567}.
CC -!- TOXIC DOSE: LD(50) is 0.4 mg/kg by intracerebroventricular injection
CC into mice. {ECO:0000269|PubMed:15225567}.
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; AY431026; AAR97287.1; -; mRNA.
DR AlphaFoldDB; Q6JK69; -.
DR SMR; Q6JK69; -.
DR Allergome; 6322; Bot at 1.
DR PRIDE; Q6JK69; -.
DR ABCD; Q6JK69; 8 sequenced antibodies.
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:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
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 Antibiotic; Antimicrobial; Cytolysis; Direct protein sequencing;
KW Disulfide bond; Myotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:15225567"
FT CHAIN 17..138
FT /note="Phospholipase A2 homolog 1"
FT /id="PRO_0000314183"
FT REGION 121..134
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="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 129
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 131
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 134
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 42..132
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..138
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 138 AA; 15583 MW; 49AEB21C9087390B CRC64;
MRTLWIMAVL LVGVEGSLVE LGKMILQETG KNPLTSYGAY GCNCGVGGRG KPKDATDRCC
YVHKCCYKKM TDCDPKKDRY SYSWKDKTIV CGEKNSCLKE LCECDKAVAI CLRENLDTYN
KKYKNNYLKP FCKKADAC
