PA2HB_AGKPI
ID PA2HB_AGKPI Reviewed; 121 AA.
AC P04361;
DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-1987, sequence version 1.
DT 25-MAY-2022, entry version 108.
DE RecName: Full=Basic phospholipase A2 homolog AppP2 {ECO:0000303|PubMed:28633930};
DE Short=svPLA2 homolog;
DE AltName: Full=APP-K49 {ECO:0000303|PubMed:28633930};
OS Agkistrodon piscivorus piscivorus (Eastern cottonmouth).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Agkistrodon.
OX NCBI_TaxID=8716;
RN [1]
RP PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=3082870; DOI=10.1016/s0021-9258(19)89175-5;
RA Maraganore J.M., Heinrikson R.L.;
RT "The lysine-49 phospholipase A2 from the venom of Agkistrodon piscivorus
RT piscivorus. Relation of structure and function to other phospholipases
RT A2.";
RL J. Biol. Chem. 261:4797-4804(1986).
RN [2]
RP PROTEIN SEQUENCE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MASS
RP SPECTROMETRY, AND IDENTIFICATION BY MASS SPECTROMETRY.
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] {ECO:0000312|PDB:1PPA}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), AND DISULFIDE BOND.
RX PubMed=2120215; DOI=10.2210/pdb1ppa/pdb;
RA Holland D.R., Clancy L.L., Muchmore S.W., Ryde T.J., Einspahr H.M.,
RA Finzel B.C., Heinrikson R.L., Watenpaugh K.D.;
RT "The crystal structure of a lysine 49 phospholipase A2 from the venom of
RT the cottonmouth snake at 2.0-A resolution.";
RL J. Biol. Chem. 265:17649-17656(1990).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND FUNCTION.
RX PubMed=1429612; DOI=10.1016/s0021-9258(18)41721-8;
RA Scott D.L., Achari A., Vidal J.C., Sigler P.B.;
RT "Crystallographic and biochemical studies of the (inactive) Lys-49
RT phospholipase A2 from the venom of Agkistridon piscivorus piscivorus.";
RL J. Biol. Chem. 267:22645-22657(1992).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that lacks enzymatic
CC activity (PubMed:1429612, PubMed:28633930). Displays edema-inducing
CC activities (PubMed:1429612). Is myotoxic (By similarity). A model of
CC myotoxic mechanism has been proposed: an apo Lys49-PLA2 is activated by
CC the entrance of a hydrophobic molecule (e.g. fatty acid) at the
CC hydrophobic channel of the protein leading to a reorientation of a
CC monomer (By similarity). This reorientation causes a transition between
CC 'inactive' to 'active' states, causing alignment of C-terminal and
CC membrane-docking sites (MDoS) side-by-side and putting the membrane-
CC disruption sites (MDiS) in the same plane, exposed to solvent and in a
CC symmetric position for both monomers (By similarity). The MDoS region
CC stabilizes the toxin on membrane by the interaction of charged residues
CC with phospholipid head groups (By similarity). Subsequently, the MDiS
CC region destabilizes the membrane with penetration of hydrophobic
CC residues (By similarity). This insertion causes a disorganization of
CC the membrane, allowing an uncontrolled influx of ions (i.e. calcium and
CC sodium), and eventually triggering irreversible intracellular
CC alterations and cell death (By similarity).
CC {ECO:0000250|UniProtKB:I6L8L6, ECO:0000250|UniProtKB:Q6JK69,
CC ECO:0000269|PubMed:1429612, ECO:0000269|PubMed:28633930}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:28633930}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28633930,
CC ECO:0000269|PubMed:3082870}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:28633930, ECO:0000305|PubMed:3082870}.
CC -!- MASS SPECTROMETRY: Mass=13948.96; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:28633930};
CC -!- TOXIC DOSE: LD(50) is 25 mg/kg by intravenous injection.
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 PIR; A00767; PSSNAM.
DR PDB; 1PPA; X-ray; 2.00 A; A=1-121.
DR PDBsum; 1PPA; -.
DR AlphaFoldDB; P04361; -.
DR SMR; P04361; -.
DR EvolutionaryTrace; P04361; -.
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 3D-structure; Direct protein sequencing; Disulfide bond; Myotoxin;
KW Secreted; Toxin.
FT CHAIN 1..121
FT /note="Basic phospholipase A2 homolog AppP2"
FT /evidence="ECO:0000269|PubMed:28633930,
FT ECO:0000269|PubMed:3082870"
FT /id="PRO_0000161606"
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 DISULFID 26..115
FT /evidence="ECO:0000269|PubMed:2120215,
FT ECO:0007744|PDB:1PPA"
FT DISULFID 28..44
FT /evidence="ECO:0000269|PubMed:2120215,
FT ECO:0007744|PDB:1PPA"
FT DISULFID 43..95
FT /evidence="ECO:0000269|PubMed:2120215,
FT ECO:0007744|PDB:1PPA"
FT DISULFID 49..121
FT /evidence="ECO:0000269|PubMed:2120215,
FT ECO:0007744|PDB:1PPA"
FT DISULFID 50..88
FT /evidence="ECO:0000269|PubMed:2120215,
FT ECO:0007744|PDB:1PPA"
FT DISULFID 57..81
FT /evidence="ECO:0000269|PubMed:2120215,
FT ECO:0007744|PDB:1PPA"
FT DISULFID 75..86
FT /evidence="ECO:0000269|PubMed:2120215,
FT ECO:0007744|PDB:1PPA"
FT HELIX 2..13
FT /evidence="ECO:0007829|PDB:1PPA"
FT HELIX 17..21
FT /evidence="ECO:0007829|PDB:1PPA"
FT TURN 25..28
FT /evidence="ECO:0007829|PDB:1PPA"
FT HELIX 39..51
FT /evidence="ECO:0007829|PDB:1PPA"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:1PPA"
FT HELIX 80..98
FT /evidence="ECO:0007829|PDB:1PPA"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:1PPA"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:1PPA"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:1PPA"
SQ SEQUENCE 121 AA; 13961 MW; 497B08243A91CA63 CRC64;
SVLELGKMIL QETGKNAITS YGSYGCNCGW GHRGQPKDAT DRCCFVHKCC YKKLTDCNHK
TDRYSYSWKN KAIICEEKNP CLKEMCECDK AVAICLRENL DTYNKKYKAY FKLKCKKPDT
C
