PA2H_PROMU
ID PA2H_PROMU Reviewed; 122 AA.
AC P22640;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 25-MAY-2022, entry version 94.
DE RecName: Full=Basic phospholipase A2 homolog;
DE Short=svPLA2 homolog;
DE AltName: Full=TMV-K49;
OS Protobothrops mucrosquamatus (Taiwan habu) (Trimeresurus mucrosquamatus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Protobothrops.
OX NCBI_TaxID=103944;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=2029535; DOI=10.1016/0167-4838(91)90552-b;
RA Liu C.-S., Chen J.-M., Chang C.-H., Chen S.-W., Teng C.-M., Tsai I.-H.;
RT "The amino acid sequence and properties of an edema-inducing Lys-49
RT phospholipase A2 homolog from the venom of Trimeresurus mucrosquamatus.";
RL Biochim. Biophys. Acta 1077:362-370(1991).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that has almost no
CC phospholipase A2 activity. Is myotoxic (By similarity). Displays edema-
CC inducing activities (PubMed:2029535). A model of myotoxic mechanism has
CC been 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:2029535}.
CC -!- SUBUNIT: Homodimer; non-covalently linked.
CC {ECO:0000250|UniProtKB:I6L8L6}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2029535}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:2029535}.
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; S15133; S15133.
DR AlphaFoldDB; P22640; -.
DR SMR; P22640; -.
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; Toxin.
FT CHAIN 1..122
FT /note="Basic phospholipase A2 homolog"
FT /evidence="ECO:0000269|PubMed:2029535"
FT /id="PRO_0000161706"
FT REGION 106..117
FT /note="Important for membrane-damaging activities in
FT eukaryotes and bacteria; heparin-binding"
FT /evidence="ECO:0000250|UniProtKB:P24605"
FT SITE 106
FT /note="Important residue of the cationic membrane-docking
FT site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 109
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 113
FT /note="Cationic membrane-docking site (MDoS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT SITE 115
FT /note="Hydrophobic membrane-disruption site (MDiS)"
FT /evidence="ECO:0000250|UniProtKB:I6L8L6"
FT DISULFID 26..116
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 28..44
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 43..96
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 49..122
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 50..89
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 57..82
FT /evidence="ECO:0000250|UniProtKB:Q90249"
FT DISULFID 75..87
FT /evidence="ECO:0000250|UniProtKB:Q90249"
SQ SEQUENCE 122 AA; 13809 MW; 96F567227B825E8B CRC64;
SLIELGKMIF QETGKNPVKN YGLYLCNCGV GNRGKPVDAT DRCCFVHKCC YKKVTGCDPK
KDRYSYSWEN KAIVCGEKNP PCLKQVCECD KAVAICLREN LQTYDKKHRV TVKFLCKAPE
SC
