A312_LOXLA
ID A312_LOXLA Reviewed; 285 AA.
AC Q1KY80;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=Dermonecrotic toxin LlSicTox-alphaIII1ii;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Ll1 {ECO:0000303|PubMed:16759681};
DE AltName: Full=Phospholipase D;
DE Short=PLD;
DE AltName: Full=Sphingomyelin phosphodiesterase D 1;
DE Short=SMD 1;
DE Short=SMase D 1;
DE Short=Sphingomyelinase D 1;
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) with high activity (56.8 U/mg) (PubMed:16759681). It
CC may also act on ceramide phosphoethanolamine (CPE),
CC lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE),
CC but not on lysophosphatidylserine (LPS), and lysophosphatidylglycerol
CC (LPG) (By similarity). It acts by transphosphatidylation, releasing
CC exclusively cyclic phosphate products as second products (By
CC similarity). Induces dermonecrosis, hemolysis, increased vascular
CC permeability, edema, inflammatory response, and platelet aggregation
CC (By similarity). Is lethal to mice (PubMed:16759681).
CC {ECO:0000250|UniProtKB:A0A0D4WTV1, ECO:0000250|UniProtKB:Q8I914,
CC 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 565 ug/kg 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; DQ369999; ABD15447.1; -; mRNA.
DR AlphaFoldDB; Q1KY80; -.
DR SMR; Q1KY80; -.
DR ArachnoServer; AS000148; Sphingomyelinase D (LlSicTox-alphaIII1ii).
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-alphaIII1ii"
FT /id="PRO_0000279579"
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; 31991 MW; A6C247F5215DB97C CRC64;
ADNRRPIWNL AHMVNAVAQI PSFLDLGANA LEADVTFKGS VPTYTYHGTP CDFGRDCIRW
EYFNVFLKTL KEYTTPGNAK YRDGFILFVL DLKTGSLSND QVRPAGENVA KELLQNYWNN
GNNGGRAYVV LSLPDIGHYE FVRGFKEVLK KEGHEDLLEK VGYDFSGPYL PSLPTLDATH
EAYKKAGVDG HIWLSDGLTN FSPLGDMARL KEAIKSRDSA NGFINKIYYW SVDKVSTTKA
ALDVGVDGIM TNHPNVLIGV LKENGYNDKY RLATYDDNPW ETFKN
