A1KB_LOXBO
ID A1KB_LOXBO Reviewed; 33 AA.
AC P0C2K0;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=Dermonecrotic toxin LbSicTox-alphaIB1b;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Lb2 {ECO:0000303|PubMed:15450925};
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;
DE Flags: Fragment;
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 PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RC TISSUE=Venom;
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).
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 (9.5 U/mg) (PubMed:15450925). 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). {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC ECO:0000250|UniProtKB:P0CE80, ECO:0000269|PubMed:15450925}.
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};
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 -!- PTM: Contains 2 disulfide bonds. {ECO:0000250|UniProtKB:P0CE80}.
CC -!- SIMILARITY: Belongs to the arthropod phospholipase D family. Class II
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}.
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 AlphaFoldDB; P0C2K0; -.
DR SMR; P0C2K0; -.
DR ArachnoServer; AS000136; Sphingomyelinase D (LbSicTox-alphaIB1b) (N-terminal fragment).
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.
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..>33
FT /note="Dermonecrotic toxin LbSicTox-alphaIB1b"
FT /id="PRO_0000279555"
FT ACT_SITE 11
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 NON_TER 33
SQ SEQUENCE 33 AA; 3655 MW; C45A65DC1AFB907D CRC64;
ANKRPVWIMA HMVNAVAQID EFVNLGANSI ETD
