PA2HB_AGKPC
ID PA2HB_AGKPC Reviewed; 121 AA.
AC C0HKC1;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 9.
DE RecName: Full=Basic phospholipase A2 homolog APC-K49 {ECO:0000303|PubMed:28633930};
DE Short=svPLA2 homolog {ECO:0000250|UniProtKB:P04361};
DE AltName: Full=ApcP2 {ECO:0000303|PubMed:28633930};
OS Agkistrodon piscivorus conanti (Florida cottonmouth).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Agkistrodon.
OX NCBI_TaxID=2782195;
RN [1]
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).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that lacks enzymatic
CC activity (PubMed:28633930). Is myotoxic and displays edema-inducing
CC activities (By similarity). A model of myotoxic mechanism has been
CC proposed: an apo Lys49-PLA2 is activated by the entrance of a
CC hydrophobic molecule (e.g. fatty acid) at the hydrophobic channel of
CC the protein leading to a reorientation of a monomer (By similarity).
CC This reorientation causes a transition between 'inactive' to 'active'
CC states, causing alignment of C-terminal and membrane-docking sites
CC (MDoS) side-by-side and putting the membrane-disruption sites (MDiS) in
CC the same plane, exposed to solvent and in a symmetric position for both
CC monomers (By similarity). The MDoS region stabilizes the toxin on
CC membrane by the interaction of charged residues with phospholipid head
CC groups (By similarity). Subsequently, the MDiS region destabilizes the
CC membrane 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}.
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:28633930}.
CC -!- MASS SPECTROMETRY: Mass=13949.23; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:28633930};
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; C0HKC1; -.
DR SMR; C0HKC1; -.
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.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Myotoxin; Secreted; Toxin.
FT CHAIN 1..121
FT /note="Basic phospholipase A2 homolog APC-K49"
FT /evidence="ECO:0000269|PubMed:28633930"
FT /id="PRO_0000439087"
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 111
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 112
FT /note="Cationic membrane-docking site (MDoS)"
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; 13961 MW; 497B08243A91CA63 CRC64;
SVLELGKMIL QETGKNAITS YGSYGCNCGW GHRGQPKDAT DRCCFVHKCC YKKLTDCNHK
TDRYSYSWKN KAIICEEKNP CLKEMCECDK AVAICLRENL DTYNKKYKAY FKLKCKKPDT
C
