A51_LOXIN
ID A51_LOXIN Reviewed; 307 AA.
AC A4USB4;
DT 14-OCT-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=Dermonecrotic toxin LiSicTox-alphaV1;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Dermonecrotic toxin 6;
DE Short=DT6 {ECO:0000303|PubMed:21590705};
DE AltName: Full=LiRecDT6 {ECO:0000303|PubMed:18082635, ECO:0000303|PubMed:21590705};
DE AltName: Full=Phospholipase D;
DE Short=PLD;
DE AltName: Full=Sphingomyelin phosphodiesterase D 6;
DE Short=SMD 6;
DE Short=SMase D 6;
DE Short=Sphingomyelinase D 6;
DE Flags: Precursor;
OS Loxosceles intermedia (Brown spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Loxosceles.
OX NCBI_TaxID=58218;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Venom gland;
RX PubMed=18082635; DOI=10.1016/j.bbagen.2007.11.007;
RA Appel M.H., da Silveira R.B., Chaim O.M., Paludo K.S., Silva D.T.,
RA Chaves D.M., da Silva P.H., Mangili O.C., Senff-Ribeiro A., Gremski W.,
RA Nader H.B., Veiga S.S.;
RT "Identification, cloning and functional characterization of a novel
RT dermonecrotic toxin (phospholipase D) from brown spider (Loxosceles
RT intermedia) venom.";
RL Biochim. Biophys. Acta 1780:167-178(2008).
RN [2]
RP FUNCTION.
RX PubMed=21590705; DOI=10.1002/jcb.23177;
RA Chaves-Moreira D., Souza F.N., Fogaca R.T., Mangili O.C., Gremski W.,
RA Senff-Ribeiro A., Chaim O.M., Veiga S.S.;
RT "The relationship between calcium and the metabolism of plasma membrane
RT phospholipids in hemolysis induced by brown spider venom phospholipase-D
RT toxin.";
RL J. Cell. Biochem. 112:2529-2540(2011).
CC -!- FUNCTION: Dermonecrotic toxins cleave the phosphodiester linkage
CC between the phosphate and headgroup of certain phospholipids
CC (sphingolipid and lysolipid substrates), forming an alcohol (often
CC choline) and a cyclic phosphate (By similarity). This toxin acts on
CC sphingomyelin (SM) with high activity (PubMed:18082635). It may also
CC act on ceramide phosphoethanolamine (CPE), lysophosphatidylcholine
CC (LPC) and lysophosphatidylethanolamine (LPE), but not on
CC lysophosphatidylserine (LPS), and lysophosphatidylglycerol (LPG) (By
CC similarity). It acts by transphosphatidylation, releasing exclusively
CC cyclic phosphate products as second products (By similarity). Induces
CC dermonecrosis, massive inflammatory response, platelet aggregation,
CC increased vascular permeability, and causes edema and death in mice
CC (PubMed:18082635). {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC ECO:0000269|PubMed:18082635}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-(acyl)-sphingosylphosphocholine = an N-(acyl)-sphingosyl-
CC 1,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60652,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:64583, ChEBI:CHEBI:143892;
CC Evidence={ECO:0000305|PubMed:18082635};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-(acyl)-sphingosylphosphoethanolamine = an N-(acyl)-
CC sphingosyl-1,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60648,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:143891, ChEBI:CHEBI:143892;
CC Evidence={ECO:0000250|UniProtKB:A0A0D4WTV1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphocholine = a 1-acyl-sn-glycero-
CC 2,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60700,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:58168, ChEBI:CHEBI:143947;
CC Evidence={ECO:0000250|UniProtKB:A0A0D4WTV1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycero-3-phosphoethanolamine = a 1-acyl-sn-
CC glycero-2,3-cyclic phosphate + ethanolamine; Xref=Rhea:RHEA:60704,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:64381, ChEBI:CHEBI:143947;
CC Evidence={ECO:0000250|UniProtKB:A0A0D4WTV1};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8I914};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q8I914};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:18082635}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:18082635}.
CC -!- SIMILARITY: Belongs to the arthropod phospholipase D family. Class II
CC subfamily. Class IIa sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: The most common activity assay for dermonecrotic toxins
CC detects enzymatic activity by monitoring choline release from
CC substrate. Liberation of choline from sphingomyelin (SM) or
CC lysophosphatidylcholine (LPC) is commonly assumed to result from
CC substrate hydrolysis, giving either ceramide-1-phosphate (C1P) or
CC lysophosphatidic acid (LPA), respectively, as a second product.
CC However, two studies from Lajoie and colleagues (2013 and 2015) report
CC the observation of exclusive formation of cyclic phosphate products as
CC second products, resulting from intramolecular transphosphatidylation.
CC Cyclic phosphates have vastly different biological properties from
CC their monoester counterparts, and they may be relevant to the pathology
CC of brown spider envenomation. {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC ECO:0000250|UniProtKB:A0A0D4WV12, ECO:0000250|UniProtKB:Q4ZFU2}.
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DR EMBL; EF474482; ABO87656.1; -; mRNA.
DR AlphaFoldDB; A4USB4; -.
DR SMR; A4USB4; -.
DR ArachnoServer; AS000019; Sphingomyelinase D (LiSicTox-alphaV1).
DR BRENDA; 3.1.4.4; 8287.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR Gene3D; 3.20.20.190; -; 1.
DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl.
DR SUPFAM; SSF51695; SSF51695; 1.
PE 1: Evidence at protein level;
KW Cytolysis; Dermonecrotic toxin; Disulfide bond; Hemolysis;
KW Lipid degradation; Lipid metabolism; Lyase; Magnesium; Metal-binding;
KW Secreted; Signal; Toxin; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..26
FT /evidence="ECO:0000250"
FT /id="PRO_0000352493"
FT CHAIN 27..307
FT /note="Dermonecrotic toxin LiSicTox-alphaV1"
FT /id="PRO_0000352494"
FT ACT_SITE 38
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 74
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 58
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 60
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 118
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT DISULFID 78..84
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 80..225
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
SQ SEQUENCE 307 AA; 35214 MW; 735749246FC11DCE CRC64;
MLCFFVLFFC CGTVLLEGAD IDEIEHADKR RPIWNMGHMV NAVYQIDEFV DLGANAIETD
VTFTKSANAE YTYHGVPCDC HRWCKKWEYV NDFLKALRRA TTPGDAKYRS QLILVVFDLK
TDYLTASTAY DAGKDFAKRL LQHYWNGGSN GGRAYIILSI PDLAHYKFIN GFKEQLKTQG
HEDLLAKVGY DFWGNEDLSS TRAAFQKAGV QDKEHIWQSD GITNCWLRTL KRVREAVANR
DSSNGYINKV YYWTVDKYAS VRDAINAGAD GIMTNYPNVI VDVLKENDFK GKFRMATYND
NPWETFK
