ID   PA2H2_CROOA             Reviewed;         121 AA.
AC   P0DUP2;
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 CoaTx-II {ECO:0000303|PubMed:27530662};
DE            Short=svPLA2 homolog;
DE   AltName: Full=Lys49 PLA2-like;
OS   Crotalus oreganus abyssus (Grand Canyon rattlesnake) (Crotalus abyssus).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Crotalus.
OX   NCBI_TaxID=128077;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, MASS
RP   SPECTROMETRY, AND 3D-STRUCTURE MODELING.
RC   TISSUE=Venom;
RX   PubMed=27530662; DOI=10.1016/j.toxicon.2016.08.007;
RA   Almeida J.R., Lancellotti M., Soares A.M., Calderon L.A., Ramirez D.,
RA   Gonzalez W., Marangoni S., Da Silva S.L.;
RT   "CoaTx-II, a new dimeric Lys49 phospholipase A2 from Crotalus oreganus
RT   abyssus snake venom with bactericidal potential: insights into its
RT   structure and biological roles.";
RL   Toxicon 120:147-158(2016).
CC   -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that lacks enzymatic
CC       inactivity (PubMed:27530662). It shows antibacterial activity against
CC       both Gram-negative and Gram-positive bacteria, including methicillin-
CC       resistant strains (PubMed:27530662). In vivo, it causes local muscular
CC       damage, but no systemic damage (intravenous administration does not
CC       elevate plasma creatine kinase). Also causes an inflammatory activity
CC       that is demonstrated by mice paw edema induction and pro-inflammatory
CC       cytokine IL-6 elevation (PubMed:27530662). 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:27530662}.
CC   -!- SUBUNIT: Homodimer; non-covalently-linked.
CC       {ECO:0000269|PubMed:27530662}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:27530662}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:27530662}.
CC   -!- MASS SPECTROMETRY: Mass=13868.2; Method=MALDI; Note=Monomeric form.;
CC       Evidence={ECO:0000269|PubMed:27530662};
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}.
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DR   AlphaFoldDB; P0DUP2; -.
DR   SMR; P0DUP2; -.
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: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.
PE   1: Evidence at protein level;
KW   Antibiotic; Antimicrobial; Direct protein sequencing; Disulfide bond;
KW   Myotoxin; Secreted; Toxin.
FT   CHAIN           1..121
FT                   /note="Basic phospholipase A2 CoaTx-II"
FT                   /id="PRO_0000452903"
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   SITE            105
FT                   /note="Important residue of the cationic membrane-docking
FT                   site (MDoS)"
FT                   /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT   SITE            108
FT                   /note="Important residue of the cationic membrane-docking
FT                   site (MDoS)"
FT                   /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT   SITE            112
FT                   /note="Cationic membrane-docking site (MDoS)"
FT                   /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT   SITE            114
FT                   /note="Hydrophobic membrane-disruption site (MDiS)"
FT                   /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT   SITE            117
FT                   /note="Cationic membrane-docking site (MDoS)"
FT                   /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT   DISULFID        26..115
FT                   /evidence="ECO:0000250|UniProtKB:Q90249"
FT   DISULFID        28..44
FT                   /evidence="ECO:0000250|UniProtKB:Q90249"
FT   DISULFID        43..95
FT                   /evidence="ECO:0000250|UniProtKB:Q90249"
FT   DISULFID        49..121
FT                   /evidence="ECO:0000250|UniProtKB:Q90249"
FT   DISULFID        50..88
FT                   /evidence="ECO:0000250|UniProtKB:Q90249"
FT   DISULFID        57..81
FT                   /evidence="ECO:0000250|UniProtKB:Q90249"
FT   DISULFID        75..86
FT                   /evidence="ECO:0000250|UniProtKB:Q90249"
SQ   SEQUENCE   121 AA;  13866 MW;  59A56475B5BDB361 CRC64;
     SLVELGKMIL QETGKNAIPS YGFYGCNCGW GGRGKPKDAT DRCCFVHKCC YKKLTDCDPK
     TDIYSYSWKN KTIICDVNNP CLKEMCECDK AVAICLRENL DTYNKKYRIY PKFLCKKPDT
     C