ID   PA2HB_AGKPL             Reviewed;         137 AA.
AC   C0HKC2;
DT   25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2017, sequence version 1.
DT   27-MAR-2024, entry version 12.
DE   RecName: Full=Basic phospholipase A2 homolog APL-K49 {ECO:0000303|PubMed:28633930};
DE            Short=svPLA2 homolog {ECO:0000250|UniProtKB:P04361};
DE   AltName: Full=AplP2 {ECO:0000303|PubMed:28633930};
DE   Flags: Precursor;
OS   Agkistrodon piscivorus leucostoma (Western cottonmouth) (Acontias
OS   leucostoma).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Viperidae; Crotalinae; Agkistrodon.
OX   NCBI_TaxID=459671;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=18502463; DOI=10.1016/j.toxicon.2008.03.028;
RA   Jia Y., Cantu B.A., Sanchez E.E., Perez J.C.;
RT   "Complementary DNA sequencing and identification of mRNAs from the venomous
RT   gland of Agkistrodon piscivorus leucostoma.";
RL   Toxicon 51:1457-1466(2008).
RN   [2]
RP   PROTEIN SEQUENCE OF 17-32, FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=28633930; DOI=10.1016/j.toxicon.2017.06.010;
RA   Jia Y., Ermolinsky B., Garza A., Provenzano D.;
RT   "Phospholipase A2 in the venom of three cottonmouth snakes.";
RL   Toxicon 135:84-92(2017).
RN   [3]
RP   FUNCTION.
RX   PubMed=29928892; DOI=10.1016/j.toxicon.2018.06.062;
RA   Jia Y., Villarreal J.;
RT   "Phospholipases A2 purified from cottonmouth snake venoms display no
RT   antibacterial effect against four representative bacterial species.";
RL   Toxicon 151:1-4(2018).
CC   -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that lacks enzymatic
CC       activity (PubMed:28633930). Does not show antibacterial activity
CC       (PubMed:29928892). Is myotoxic and displays edema-inducing activities
CC       (By similarity). A model of myotoxic mechanism has been proposed: an
CC       apo Lys49-PLA2 is activated by the entrance of a hydrophobic molecule
CC       (e.g. fatty acid) at the hydrophobic channel of the protein leading to
CC       a reorientation of a monomer (By similarity). This reorientation causes
CC       a transition between 'inactive' to 'active' states, causing alignment
CC       of C-terminal and membrane-docking sites (MDoS) side-by-side and
CC       putting the membrane-disruption sites (MDiS) in the same plane, exposed
CC       to solvent and in a symmetric position for both monomers (By
CC       similarity). The MDoS region stabilizes the toxin on membrane by the
CC       interaction of charged residues with phospholipid head groups (By
CC       similarity). Subsequently, the MDiS region destabilizes the membrane
CC       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:0000269|PubMed:28633930, ECO:0000269|PubMed:29928892}.
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:28633930}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28633930}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:18502463}.
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 ligands 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; EV854871; -; NOT_ANNOTATED_CDS; mRNA.
DR   AlphaFoldDB; C0HKC2; -.
DR   SMR; C0HKC2; -.
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; Phospholipase A2 domain; 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:SF57; GROUP IID SECRETORY PHOSPHOLIPASE A2; 1.
DR   PANTHER; PTHR11716; PHOSPHOLIPASE A2 FAMILY MEMBER; 1.
DR   Pfam; PF00068; Phospholip_A2_1; 1.
DR   PRINTS; PR00389; PHPHLIPASEA2.
DR   SMART; SM00085; PA2c; 1.
DR   SUPFAM; SSF48619; Phospholipase A2, PLA2; 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:28633930"
FT   CHAIN           17..137
FT                   /note="Basic phospholipase A2 homolog APL-K49"
FT                   /evidence="ECO:0000305|PubMed:28633930"
FT                   /id="PRO_0000442173"
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            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;  15713 MW;  3D8FC7C0E4B5AA8D CRC64;
     MRTLWIVALL LVGVEGSVLE LGKMILQETG KNAITSYGSY GCNCGWGHRG QPKDATDRCC
     FVHKCCYKKL TDCNHKTDRY SYSWKNKAII CEEKNPCLKE MCECDKAVAI CLRENLDTYN
     KKYKAYFKLK CKKPDTC
//