A1KA_LOXBO
ID A1KA_LOXBO Reviewed; 279 AA.
AC Q5YD77;
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 LbSicTox-alphaIB1a;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Lb1 {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 boneti (North American fiddleback spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Loxosceles.
OX NCBI_TaxID=283164;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-35, FUNCTION, SUBCELLULAR
RP LOCATION, AND CATALYTIC ACTIVITY.
RC TISSUE=Venom, and 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 (about 30.5-31.5 U/mg)
CC (PubMed:15450925, PubMed:16759681). It may also act on ceramide
CC 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:15450925,
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:15450925, 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:0000269|PubMed:15450925}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:15450925}.
CC -!- TOXIC DOSE: LD(50) is 200-250 ug/kg by intraperitoneal injection into
CC mice. {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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY559844; AAT66073.1; -; mRNA.
DR AlphaFoldDB; Q5YD77; -.
DR SMR; Q5YD77; -.
DR ArachnoServer; AS000519; Sphingomyelinase D (LbSicTox-alphaIB1a).
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; Direct protein sequencing; Disulfide bond;
KW Hemolysis; Lipid degradation; Lipid metabolism; Lyase; Magnesium;
KW Metal-binding; Secreted; Toxin.
FT CHAIN 1..279
FT /note="Dermonecrotic toxin LbSicTox-alphaIB1a"
FT /id="PRO_0000279554"
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"
FT CONFLICT 6
FT /note="A -> V (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 279 AA; 30997 MW; DB34384AB755A847 CRC64;
ANKRPAWIMG HMVNAIAQID EFVNLGANSI ETDVSFDSSA NPEYTYHGIP CDCGRTCTKW
ENFNDFLVGL RKATTPDDSN YHEKLILVVF DLKTGSLYDN QAYDAGKKLA KSILQHYWNN
GNNGGRAYIV LSIPNLAHYK LITGFKETLT SDGHPELMDK IGYDFSGNDA IGDVASAYQK
AGVTGHVWQS DGITNCLLRG LSRVREAVAN RDSSNGYINK VYYWTVDKRA STRDALDAGV
DGIMTNYPDV IADVLSESAY SAKFRIATYD DNPWETFKN
