PA22_OXYSC
ID PA22_OXYSC Reviewed; 146 AA.
AC Q45Z47;
DT 09-JAN-2013, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2013, sequence version 2.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Phospholipase A2 OS2;
DE Short=PLA2;
DE EC=3.1.1.4;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE Flags: Precursor;
OS Oxyuranus scutellatus scutellatus (Australian taipan) (Coastal taipan).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Acanthophiinae; Oxyuranus.
OX NCBI_TaxID=8667;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=16261251; DOI=10.1007/s00018-005-5384-9;
RA St Pierre L., Woods R., Earl S.T.H., Masci P.P., Lavin M.F.;
RT "Identification and analysis of venom gland-specific genes from the coastal
RT taipan (Oxyuranus scutellatus) and related species.";
RL Cell. Mol. Life Sci. 62:2679-2693(2005).
RN [2]
RP PROTEIN SEQUENCE OF 28-146.
RC TISSUE=Venom;
RX PubMed=7890672; DOI=10.1074/jbc.270.10.5534;
RA Lambeau G., Ancian P., Nicolas J.P., Beiboer S.H., Moinier D., Verheij H.,
RA Lazdunski M.;
RT "Structural elements of secretory phospholipases A2 involved in the binding
RT to M-type receptors.";
RL J. Biol. Chem. 270:5534-5540(1995).
RN [3]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=2544597; DOI=10.1016/s0021-9258(18)60492-2;
RA Lambeau G., Barhanin J., Schweitz H., Qar J., Lazdunski M.;
RT "Identification and properties of very high affinity brain membrane-binding
RT sites for a neurotoxic phospholipase from the taipan venom.";
RL J. Biol. Chem. 264:11503-11510(1989).
RN [4]
RP FUNCTION, AND SUBUNIT.
RC TISSUE=Venom;
RX PubMed=2160984; DOI=10.1016/s0021-9258(19)38881-7;
RA Lambeau G., Schmid-Alliana A., Lazdunski M., Barhanin J.;
RT "Identification and purification of a very high affinity binding protein
RT for toxic phospholipases A2 in skeletal muscle.";
RL J. Biol. Chem. 265:9526-9532(1990).
RN [5]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=8583413; DOI=10.1113/jphysiol.1995.sp021027;
RA Fossier P., Lambeau G., Lazdunski M., Baux G.;
RT "Inhibition of ACh release at an Aplysia synapse by neurotoxic
RT phospholipases A2: specific receptors and mechanisms of action.";
RL J. Physiol. (Lond.) 489:29-40(1995).
RN [6]
RP FUNCTION, AND BIOASSAY.
RC TISSUE=Venom;
RX PubMed=10548416; DOI=10.1016/s0304-3940(99)00709-0;
RA Kolko M., Bruhn T., Christensen T., Lazdunski M., Lambeau G., Bazan N.G.,
RA Diemer N.H.;
RT "Secretory phospholipase A2 potentiates glutamate-induced rat striatal
RT neuronal cell death in vivo.";
RL Neurosci. Lett. 274:167-170(1999).
RN [7]
RP FUNCTION.
RX PubMed=12782627; DOI=10.1074/jbc.m211763200;
RA Beck S., Lambeau G., Scholz-Pedretti K., Gelb M.H., Janssen M.J.,
RA Edwards S.H., Wilton D.C., Pfeilschifter J., Kaszkin M.;
RT "Potentiation of tumor necrosis factor alpha-induced secreted phospholipase
RT A2 (sPLA2)-IIA expression in mesangial cells by an autocrine loop involving
RT sPLA2 and peroxisome proliferator-activated receptor alpha activation.";
RL J. Biol. Chem. 278:29799-29812(2003).
RN [8]
RP FUNCTION, TOXIC DOSE, AND MUTAGENESIS OF GLY-57; HIS-75 AND ASP-76.
RX PubMed=16669624; DOI=10.1021/bi060217r;
RA Rouault M., Rash L.D., Escoubas P., Boilard E., Bollinger J., Lomonte B.,
RA Maurin T., Guillaume C., Canaan S., Deregnaucourt C., Schrevel J.,
RA Doglio A., Gutierrez J.M., Lazdunski M., Gelb M.H., Lambeau G.;
RT "Neurotoxicity and other pharmacological activities of the snake venom
RT phospholipase A2 OS2: the N-terminal region is more important than
RT enzymatic activity.";
RL Biochemistry 45:5800-5816(2006).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that shows high
CC presynaptic neurotoxicity in vertebrata that is independent of
CC catalytic activity (PubMed:2544597, PubMed:10548416 and
CC PubMed:16669624), as well as local myotoxicity when intramuscularly
CC injected into mice (PubMed:16669624). Blocks acetylcholine release in
CC Aplysia neurons (PubMed:8583413), and potentiates pro-inflammatory
CC cellular signaling (PubMed:12782627). Potentiates glutamate
CC excitoxicity when coinjected into brain of rats (PubMed:10548416). May
CC act by binding in a calcium-dependent fashion and with high affinity to
CC a neuronal-type (N-type) PLA2 receptor, and with very high affinity to
CC a muscle-type (M-type) PLA2 receptor. In vitro, shows a high-specific
CC activity on E.coli membranes and is more efficient on the anionic
CC phospholipid POPG than on the anionic phospholipid POPS or the
CC zwitterionic phospholipid POPC. Exerts catalytically-independent anti-
CC HIV (IC(50) is 35 nM) activity and catalytically-dependent antimalarial
CC activity (IC(50) is 3.1 nM when tested on P.falciparum grown in serum
CC that contains lipoproteins). PLA2 catalyzes the calcium-dependent
CC hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
CC {ECO:0000269|PubMed:10548416, ECO:0000269|PubMed:12782627,
CC ECO:0000269|PubMed:16669624, ECO:0000269|PubMed:2160984,
CC ECO:0000269|PubMed:2544597, ECO:0000269|PubMed:8583413}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10035, ECO:0000255|PROSITE-
CC ProRule:PRU10036};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000250};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:2160984}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- TOXIC DOSE: LD(100) is 2 ug/kg by intracerebroventricular injection
CC into mice. {ECO:0000269|PubMed:16669624}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group I subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR EMBL; DQ085819; AAZ22637.1; -; mRNA.
DR AlphaFoldDB; Q45Z47; -.
DR SMR; Q45Z47; -.
DR PRIDE; Q45Z47; -.
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:UniProtKB-EC.
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:UniProtKB-KW.
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 Calcium; Direct protein sequencing; Disulfide bond; Hydrolase;
KW Lipid degradation; Lipid metabolism; Metal-binding; Myotoxin; Neurotoxin;
KW Presynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..146
FT /note="Phospholipase A2 OS2"
FT /id="PRO_5000140344"
FT ACT_SITE 75
FT /evidence="ECO:0000250"
FT ACT_SITE 120
FT /evidence="ECO:0000250"
FT BINDING 55
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 57
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 59
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 76
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT DISULFID 38..99
FT /evidence="ECO:0000250"
FT DISULFID 54..145
FT /evidence="ECO:0000250"
FT DISULFID 56..72
FT /evidence="ECO:0000250"
FT DISULFID 71..126
FT /evidence="ECO:0000250"
FT DISULFID 78..119
FT /evidence="ECO:0000250"
FT DISULFID 88..112
FT /evidence="ECO:0000250"
FT DISULFID 106..117
FT /evidence="ECO:0000250"
FT MUTAGEN 57
FT /note="G->S: Large decrease in neurotoxicity, 500-fold
FT decrease in catalytic activity, no change in binding
FT affinity to M-type receptors, 20'000-fold decrease in
FT binding affinity to N-type receptors."
FT /evidence="ECO:0000269|PubMed:16669624"
FT MUTAGEN 58
FT /note="K->L: Almost no decrease in neurotoxicity,
FT myotoxicity, nor in catalytic activity, no change in
FT binding affinity to M-type receptors, no important decrease
FT in binding affinity to N-type receptors; when associated
FT with L-58."
FT MUTAGEN 61
FT /note="R->S: Almost no decrease in neurotoxicity,
FT myotoxicity, nor in catalytic activity, no change in
FT binding affinity to M-type receptors, no important decrease
FT in binding affinity to N-type receptors; when associated
FT with L-58."
FT MUTAGEN 75
FT /note="H->Q: 16-fold decrease in neurotoxicity, 500-fold
FT decrease in catalytic activity, no change in binding
FT affinity to M-type receptors, 50-fold decrease in binding
FT affinity to N-type receptors."
FT /evidence="ECO:0000269|PubMed:16669624"
FT MUTAGEN 76
FT /note="D->K: Complete loss of neurotoxicity and catalytic
FT activity, no change in binding affinity to M-type
FT receptors, 1230-fold decrease in binding affinity to N-type
FT receptors."
FT /evidence="ECO:0000269|PubMed:16669624"
FT CONFLICT 61
FT /note="R -> S (in Ref. 1; AAZ22637)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 146 AA; 16104 MW; BAC536B8C8DB281A CRC64;
MHPAHLLVLL AVCVSLLGAS DIPPLPLNLA QFGFMIRCAN GGSRSPLDYT DYGCYCGKGG
RGTPVDDLDR CCQVHDECYG EAEKRLGCSP FVTLYSWKCY GKAPSCNTKT DCQRFVCNCD
AKAAECFARS PYQKKNWNIN TKARCK
