A1K_LOXRE
ID A1K_LOXRE Reviewed; 279 AA.
AC Q5YD75;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=Dermonecrotic toxin LrSicTox-alphaIB1;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Lr1 {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 reclusa (Brown recluse spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Loxosceles.
OX NCBI_TaxID=6921;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=15450925; DOI=10.1016/j.toxicon.2004.06.013;
RA Ramos-Cerrillo B., Olvera A., Odell G.V., Zamudio F., Paniagua-Solis J.,
RA Alagon A., Stock R.P.;
RT "Genetic and enzymatic characterization of sphingomyelinase D isoforms from
RT the North American fiddleback spiders Loxosceles boneti and Loxosceles
RT reclusa.";
RL Toxicon 44:507-514(2004).
RN [2]
RP FUNCTION, TOXIC DOSE, AND CATALYTIC ACTIVITY.
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 (18.3 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:P0CE80,
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:15450925}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:15450925}.
CC -!- TOXIC DOSE: LD(50) is 175 ug/kg by intraperitoneal injection into mice.
CC {ECO:0000269|PubMed:16759681}.
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; AY559846; AAT66075.1; -; mRNA.
DR AlphaFoldDB; Q5YD75; -.
DR SMR; Q5YD75; -.
DR ArachnoServer; AS000133; Sphingomyelinase D (LrSicTox-alphaIB1).
DR BRENDA; 3.1.4.41; 3077.
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..279
FT /note="Dermonecrotic toxin LrSicTox-alphaIB1"
FT /id="PRO_0000279581"
FT ACT_SITE 11
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 47
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 31
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 33
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:P0CE80"
FT DISULFID 53..196
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
SQ SEQUENCE 279 AA; 31202 MW; 8619EA9AFA5EEC82 CRC64;
ANKRPAWIMG HMVNAVAQID EFVNLGANSI ETDVSFDKNA NPEYTYHGIP CDCGRTCTKW
ENFNDFLKGL RKATTPGDSK YHEKLVLVVF DLKTGSLYDN QAYDAGKKLA KNILQHYWNN
GNNGGRAYIV LSIPNLAHYK LITGFKETLT SEGHPELMEK VGYDFSGNDD IDKVGNAYKN
AGVTGHVWQS DGITNCLLRG LSRVKEAVKN RDSSNGFINK VYFWTVDKRA STRDALDAGV
DGIMTNYPDV IADVLSESAY KANFRIATYD DNPWETFKN
