A32_LOXLA
ID A32_LOXLA Reviewed; 285 AA.
AC Q1KY79;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Dermonecrotic toxin LlSicTox-alphaIII2;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Ll2 {ECO:0000303|PubMed:16759681};
DE AltName: Full=Phospholipase D;
DE Short=PLD;
DE AltName: Full=Sphingomyelin phosphodiesterase D 2;
DE Short=SMD 2;
DE Short=SMase D 2;
DE Short=Sphingomyelinase D 2;
OS Loxosceles laeta (South American recluse spider) (Scytodes laeta).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Loxosceles.
OX NCBI_TaxID=58217;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TOXIC DOSE, AND CATALYTIC ACTIVITY.
RC TISSUE=Venom gland;
RX PubMed=16759681; DOI=10.1016/j.toxicon.2006.04.010;
RA Olvera A., Ramos-Cerrillo B., Estevez J., Clement H., de Roodt A.,
RA Paniagua-Solis J., Vazquez H., Zavaleta A., Arruz M.S., Stock R.P.,
RA Alagon A.;
RT "North and south american Loxosceles spiders: development of a polyvalent
RT antivenom with recombinant sphingomyelinases D as antigens.";
RL Toxicon 48:64-74(2006).
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) (228.2 U/mg) (PubMed:16759681). It may also act on
CC ceramide phosphoethanolamine (CPE), lysophosphatidylcholine (LPC) and
CC lysophosphatidylethanolamine (LPE), but not on lysophosphatidylserine
CC (LPS), and lysophosphatidylglycerol (LPG) (By similarity). It acts by
CC transphosphatidylation, releasing exclusively cyclic phosphate products
CC as second products (By similarity). Induces dermonecrosis, hemolysis,
CC increased vascular permeability, edema, inflammatory response, and
CC platelet aggregation (By similarity). Is lethal to mice
CC (PubMed:16759681). {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC ECO:0000250|UniProtKB:P0CE80, ECO:0000269|PubMed:16759681}.
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:16759681};
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:16759681}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:16759681}.
CC -!- TOXIC DOSE: LD(50) is 118.5 by intraperitoneal injection into mice.
CC {ECO:0000269|PubMed:16759681}.
CC -!- SIMILARITY: Belongs to the arthropod phospholipase D family. Class I
CC 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; DQ370000; ABD15448.1; -; mRNA.
DR AlphaFoldDB; Q1KY79; -.
DR SMR; Q1KY79; -.
DR ArachnoServer; AS000150; Sphingomyelinase D (LlSicTox-alphaIII2).
DR BRENDA; 3.1.4.41; 6922.
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; Toxin.
FT CHAIN 1..285
FT /note="Dermonecrotic toxin LlSicTox-alphaIII2"
FT /id="PRO_0000279580"
FT ACT_SITE 12
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 47
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 32
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 91
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT DISULFID 51..57
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
SQ SEQUENCE 285 AA; 32551 MW; BDEDB64DEE0F29BA CRC64;
ADNRRPIWNL GHMVNAVKQI PTFLNDGANA IEADITFKGA VPTYSYHGTP CDFGRDCIRW
EYFDVFLRTL REYTTPGNSK YREKFILFVL DLKTGSLNNH EVRKAGENVA KGLLENYWNN
GNNGGRAYVV LSLPDIAHYE FIRTFKEVLK TAGHENLLDK VGYDLSGPYW PSLPSLDSVH
EAFKKAGVDG HVWLSDGLTN WAKLGDMARL KEIIKSRDSE NGFISKVYYW SVDKYSTTRT
ALDVGVDGIM TNYPYVIIDV LNENGYKDKY RLATYDDNPW ETFKN
