PA2HB_AGKPL
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 25-MAY-2022, entry version 9.
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; -; 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: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
