PA2BB_VIPAA
ID PA2BB_VIPAA Reviewed; 138 AA.
AC P14424; Q91521;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 2.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Basic phospholipase A2 ammodytoxin B;
DE Short=AtxB;
DE Short=svPLA2;
DE EC=3.1.1.4;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE Flags: Precursor;
OS Vipera ammodytes ammodytes (Western sand viper).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Vipera.
OX NCBI_TaxID=8705;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Northern Balkan; TISSUE=Venom gland;
RX PubMed=2374735; DOI=10.1093/nar/18.13.4016;
RA Kordis D., Pungercar J., Strukelj B., Liang N.-S., Gubensek F.;
RT "Sequence of the cDNA coding for ammodytoxin B.";
RL Nucleic Acids Res. 18:4016-4016(1990).
RN [2]
RP PROTEIN SEQUENCE OF 17-138.
RC STRAIN=Northern Balkan; TISSUE=Venom;
RX PubMed=3790259; DOI=10.1515/bchm3.1986.367.2.919;
RA Ritonja A., Machleidt W., Turk V., Gubensek F.;
RT "Amino-acid sequence of ammodytoxin B partially reveals the location of the
RT site of toxicity of ammodytoxins.";
RL Biol. Chem. Hoppe-Seyler 367:919-923(1986).
RN [3]
RP REVIEW, AND TOXIC DOSE.
RX PubMed=21726572; DOI=10.1016/j.toxicon.2011.06.009;
RA Krizaj I.;
RT "Ammodytoxin: a window into understanding presynaptic toxicity of secreted
RT phospholipases A(2) and more.";
RL Toxicon 58:219-229(2011).
RN [4]
RP CATALYTIC ACTIVITY, COFACTOR, AND SITE.
RX PubMed=16156665; DOI=10.1021/bi051024r;
RA Petan T., Krizaj I., Gelb M.H., Pungercar J.;
RT "Ammodytoxins, potent presynaptic neurotoxins, are also highly efficient
RT phospholipase A2 enzymes.";
RL Biochemistry 44:12535-12545(2005).
RN [5]
RP FUNCTION, AND BINDING TO COAGULATION FACTOR X (F10).
RX PubMed=16039772; DOI=10.1016/j.biochi.2005.06.015;
RA Prijatelj P., Charnay M., Ivanovski G., Jenko Z., Pungercar J., Krizaj I.,
RA Faure G.;
RT "The C-terminal and beta-wing regions of ammodytoxin A, a neurotoxic
RT phospholipase A2 from Vipera ammodytes ammodytes, are critical for binding
RT to factor Xa and for anticoagulant effect.";
RL Biochimie 88:69-76(2006).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that acts as a
CC presynaptic neurotoxin, an inhibitor of blood coagulation, and has been
CC found to bind with high affinity to intracellular proteins. The
CC response of indirectly stimulated neuromuscular preparations to
CC ammodytoxin (Atx) is triphasic. The first phase, the transient
CC inhibition of the acetylcholine (ACh) release, starts soon after the
CC addition of Atx and lasts for several minutes. This phase is probably
CC independent of Atx enzymatic activity. The effect may be due to the
CC specific binding of the toxin to presynaptic receptors. These
CC receptors, called N-type receptors, are still unidentified. It is
CC noteworthy that a neuronal isoform of the M-type PLA2 receptor (R180)
CC has been identified as a high-affinity receptor for Atx in neuronal
CC plasma membranes. It was demonstrated however that this receptor is not
CC essential for expression of neurotoxicity by Atx. The second phase
CC corresponds to an augmentation of neurotransmitter release. A peak is
CC reached 10-20 min after exposure of the preparation to Atx and is
CC followed by a gradual reduction. In this phase, the enzymatic activity
CC of Atx of the mammalian is not significant. It is speculated that the
CC increased release of neurotransmitter in this phase is induced by the
CC interference of Atx with voltage-gated potassium channels. Measurements
CC of ionic currents showed however that voltage-gated potassium channels
CC are not affected by Atx. The third phase of the response of
CC neuromuscular preparations to Atx, which corresponds to a complete and
CC irreversible paralysis, is clearly dependent on the hydrolytic activity
CC of the toxin. In addition to its presynaptic neurotoxicity, Atx shows
CC an anticoagulant activity by binding with high affinity to activated
CC coagulation factor X (F10) thus inhibiting the formation of the
CC prothrombinase complex (FX/FV) and its activity (IC(50) is 82 nM).
CC Surprisingly, Atx was discovered to bind intracellular proteins such as
CC calmodulin (CaM), 14-3-3 proteins gamma (YWHAG) and epsilon (YWHAE) (by
CC similarity with AtxC), as well as R25 (by similarity with AtxC), a
CC mitochondrial integral membrane protein found in cerebral cortex. These
CC findings raised a doubt about the dogma of the exclusively
CC extracellular action of PLA2s, defended by the potential instability of
CC these molecules in the reducing environment of the eukaryotic cytosol
CC coupled with their possible inability to act as enzymes in this
CC cellular compartment, due to too low concentration of calcium ions.
CC This hypothesis was challenged efficiently by demonstrating the
CC internalization of AtxA into a culture cells, but still remains to be
CC directly demonstrated in vivo (By similarity). PLA2 catalyzes the
CC calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-
CC phosphoglycerides. {ECO:0000250, ECO:0000269|PubMed:16039772}.
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, ECO:0000269|PubMed:16156665};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:16156665};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000269|PubMed:16156665};
CC -!- SUBUNIT: Monomer. Binds to calmodulin, coagulation factor X (F10), M-
CC type PLA2 receptor (R-180), 14-3-3 proteins gamma (YWHAG) and epsilon
CC (YWHAE), and R25, a mitochondrial membrane protein (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted. Host cytoplasm, host cytosol
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- TOXIC DOSE: LD(50) is 0.58 mg/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:21726572}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR EMBL; X52241; CAA36486.1; -; mRNA.
DR EMBL; X52241; CAA36487.1; -; mRNA.
DR PIR; A25806; A25806.
DR PIR; S10333; S10333.
DR AlphaFoldDB; P14424; -.
DR SMR; P14424; -.
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 Blood coagulation cascade inhibiting toxin; Calcium;
KW Direct protein sequencing; Disulfide bond; Hemostasis impairing toxin;
KW Host cytoplasm; Hydrolase; Lipid degradation; Lipid metabolism;
KW Metal-binding; Neurotoxin; Presynaptic neurotoxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:3790259"
FT CHAIN 17..138
FT /note="Basic phospholipase A2 ammodytoxin B"
FT /evidence="ECO:0000269|PubMed:3790259"
FT /id="PRO_0000022971"
FT ACT_SITE 63
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT ACT_SITE 105
FT /evidence="ECO:0000250|UniProtKB:P14418"
FT BINDING 43
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT BINDING 45
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT BINDING 47
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT SITE 18
FT /note="Putative membrane binding site"
FT SITE 19
FT /note="Putative membrane binding site"
FT SITE 34
FT /note="Putative membrane binding site"
FT SITE 35
FT /note="Putative membrane binding site"
FT SITE 39
FT /note="Putative membrane binding site"
FT SITE 46
FT /note="Putative membrane binding site"
FT SITE 76
FT /note="Putative membrane binding site"
FT SITE 77
FT /note="Putative membrane binding site"
FT SITE 79
FT /note="Putative membrane binding site"
FT SITE 82
FT /note="Putative membrane binding site"
FT SITE 124
FT /note="Putative membrane binding site"
FT SITE 125
FT /note="Putative membrane binding site"
FT SITE 129
FT /note="Putative membrane binding site"
FT DISULFID 42..131
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT DISULFID 44..60
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT DISULFID 59..111
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT DISULFID 65..138
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT DISULFID 66..104
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT DISULFID 73..97
FT /evidence="ECO:0000250|UniProtKB:P59071"
FT DISULFID 91..102
FT /evidence="ECO:0000250|UniProtKB:P59071"
SQ SEQUENCE 138 AA; 15529 MW; D9E6987A04F18811 CRC64;
MRTLWIVAVC LIGVEGSLLE FGMMILGETG KNPLTSYSFY GCYCGVGGKG TPKDATDRCC
FVHDCCYGNL PDCSPKTDRY KYHRENGAIV CGKGTSCENR ICECDRAAAI CFRKNLKTYN
HIYMYYPDFL CKKESEKC
