PA2B_NOTSC
ID PA2B_NOTSC Reviewed; 119 AA.
AC P00608;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Basic phospholipase A2 notexin {ECO:0000303|PubMed:1158892};
DE Short=svPLA2;
DE EC=3.1.1.4;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
OS Notechis scutatus scutatus (Mainland tiger snake) (Common tiger snake).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Acanthophiinae; Notechis.
OX NCBI_TaxID=70142;
RN [1]
RP PROTEIN SEQUENCE.
RC TISSUE=Venom;
RX PubMed=1158892; DOI=10.1016/s0021-9258(19)41030-2;
RA Halpert J., Eaker D.;
RT "Amino acid sequence of a presynaptic neurotoxin from the venom of Notechis
RT scutatus scutatus (Australian tiger snake).";
RL J. Biol. Chem. 250:6990-6997(1975).
RN [2]
RP PROTEIN SEQUENCE (NOTEXIN-S).
RC TISSUE=Venom;
RX PubMed=2155818; DOI=10.1016/0014-5793(90)80559-2;
RA Chwetzoff S., Mollier P., Bouet F., Rowan E.G., Harvey A.L., Menez A.;
RT "On the purification of notexin. Isolation of a single amino acid variant
RT from the venom of Notechis scutatus scutatus.";
RL FEBS Lett. 261:226-230(1990).
RN [3]
RP ACTIVE SITE.
RX PubMed=1245225; DOI=10.1016/0014-5793(76)80174-3;
RA Halpert J., Eaker D., Karlsson E.;
RT "The role of phospholipase activity in the action of a presynaptic
RT neurotoxin from the venom of Notechis scutatus scutatus (Australian tiger
RT snake).";
RL FEBS Lett. 61:72-76(1976).
RN [4]
RP INVOLVEMENT OF TRP-110 IN TOXICITY.
RX PubMed=2583182; DOI=10.1111/j.1432-1033.1989.tb15111.x;
RA Mollier P., Chwetzoff S., Bouet F., Harvey A.L., Menez A.;
RT "Tryptophan 110, a residue involved in the toxic activity but not in the
RT enzymatic activity of notexin.";
RL Eur. J. Biochem. 185:263-270(1989).
RN [5]
RP FUNCTION AS NEPHROTOXIN.
RC TISSUE=Venom;
RX PubMed=7580101; DOI=10.1016/s0940-2993(11)80305-2;
RA Zimmerman S.E., Yong L.C.;
RT "Nephrotoxicity of notexin in experimental mice.";
RL Exp. Toxicol. Pathol. 47:149-155(1995).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), AND DISULFIDE BONDS.
RX PubMed=1568473; DOI=10.1016/0014-5793(92)81238-h;
RA Westerlund B., Nordlund P., Uhlim U., Eaker D., Eklund H.;
RT "The three-dimensional structure of notexin, a presynaptic neurotoxic
RT phospholipase A2 at 2.0-A resolution.";
RL FEBS Lett. 301:159-164(1992).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that inhibits
CC neuromuscular transmission by blocking acetylcholine release from the
CC nerve termini. Is directly toxic to skeletal muscle upon local
CC application in vivo (dystrophic effect). Also has direct nephrotoxicity
CC in experimental mice; a single subcutaneous dose (1.38 ug/kg) produces
CC renal tubular and glomerular damage within 24 hours (PubMed:7580101).
CC PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in
CC 3-sn-phosphoglycerides.
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;
CC Evidence={ECO:0000250|UniProtKB:P60043};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000250|UniProtKB:P60043};
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- TOXIC DOSE: LD(50) is 0.025 mg/kg by intravenous injection.
CC -!- MISCELLANEOUS: Activity and lethal neurotoxicity are lost upon
CC modification with p-bromophenacyl bromide.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group I subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR PIR; A00749; PSNOAT.
DR PIR; S08258; PSNOAS.
DR PDB; 1AE7; X-ray; 2.00 A; A=1-119.
DR PDB; 4E4C; X-ray; 1.80 A; A=1-119.
DR PDBsum; 1AE7; -.
DR PDBsum; 4E4C; -.
DR AlphaFoldDB; P00608; -.
DR SMR; P00608; -.
DR EvolutionaryTrace; P00608; -.
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 3D-structure; Calcium; Direct protein sequencing; Disulfide bond;
KW Hydrolase; Lipid degradation; Lipid metabolism; Metal-binding; Myotoxin;
KW Neurotoxin; Presynaptic neurotoxin; Secreted; Toxin.
FT CHAIN 1..119
FT /note="Basic phospholipase A2 notexin"
FT /id="PRO_0000161675"
FT ACT_SITE 48
FT /evidence="ECO:0000269|PubMed:1245225"
FT ACT_SITE 93
FT /evidence="ECO:0000269|PubMed:1245225"
FT BINDING 28
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P60043"
FT BINDING 30
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P60043"
FT BINDING 32
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P60043"
FT BINDING 49
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P60043"
FT DISULFID 11..71
FT /evidence="ECO:0000269|PubMed:1568473,
FT ECO:0007744|PDB:1AE7"
FT DISULFID 27..118
FT /evidence="ECO:0000269|PubMed:1568473,
FT ECO:0007744|PDB:1AE7"
FT DISULFID 29..45
FT /evidence="ECO:0000269|PubMed:1568473,
FT ECO:0007744|PDB:1AE7"
FT DISULFID 44..99
FT /evidence="ECO:0000269|PubMed:1568473,
FT ECO:0007744|PDB:1AE7"
FT DISULFID 51..92
FT /evidence="ECO:0000269|PubMed:1568473,
FT ECO:0007744|PDB:1AE7"
FT DISULFID 60..85
FT /evidence="ECO:0000269|PubMed:1568473,
FT ECO:0007744|PDB:1AE7"
FT DISULFID 78..90
FT /evidence="ECO:0000269|PubMed:1568473,
FT ECO:0007744|PDB:1AE7"
FT VARIANT 16
FT /note="K -> R (in variant S)"
FT HELIX 2..12
FT /evidence="ECO:0007829|PDB:4E4C"
FT TURN 13..15
FT /evidence="ECO:0007829|PDB:4E4C"
FT HELIX 19..22
FT /evidence="ECO:0007829|PDB:4E4C"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:4E4C"
FT TURN 26..28
FT /evidence="ECO:0007829|PDB:4E4C"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:4E4C"
FT HELIX 40..57
FT /evidence="ECO:0007829|PDB:4E4C"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:4E4C"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:4E4C"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:4E4C"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:1AE7"
FT HELIX 84..102
FT /evidence="ECO:0007829|PDB:4E4C"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:4E4C"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:4E4C"
SQ SEQUENCE 119 AA; 13593 MW; 23D8BF780221D852 CRC64;
NLVQFSYLIQ CANHGKRPTW HYMDYGCYCG AGGSGTPVDE LDRCCKIHDD CYDEAGKKGC
FPKMSAYDYY CGENGPYCRN IKKKCLRFVC DCDVEAAFCF AKAPYNNANW NIDTKKRCQ
