A31_LOXLA
ID A31_LOXLA Reviewed; 311 AA.
AC E5D3Z8;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 1.
DT 03-AUG-2022, entry version 33.
DE RecName: Full=Dermonecrotic toxin;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Phospholipase D isoform 1;
DE Short=LlPLD1 {ECO:0000303|PubMed:21692149};
DE Short=PLD1;
DE AltName: Full=Sphingomyelin phosphodiesterase D;
DE Short=SMD;
DE Short=SMase D;
DE Short=Sphingomyelinase D;
DE Flags: Precursor;
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], AND FUNCTION.
RC TISSUE=Venom gland;
RX PubMed=21692149; DOI=10.1002/jbt.20399;
RA Catalan A., Cortes W., Sagua H., Gonzalez J., Araya J.E.;
RT "Two new phospholipase D isoforms of Loxosceles laeta: cloning,
RT heterologous expression, functional characterization, and potential
RT biotechnological application.";
RL J. Biochem. Mol. Toxicol. 25:393-403(2011).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TRP-256; SER-257; ASP-259;
RP SER-262 AND ASP-269.
RX PubMed=24472346; DOI=10.1016/j.toxicon.2014.01.011;
RA Catalan A., Cortes W., Munoz C., Araya J.E.;
RT "Tryptophan and aspartic acid residues present in the glycerophosphoryl
RT diester phosphodiesterase (GDPD) domain of the Loxosceles laeta
RT phospholipase D are essential for substrate recognition.";
RL Toxicon 81:43-47(2014).
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) (PubMed:24472346). 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). Shows complement-dependent
CC hemolysis (PubMed:21692149). Also induces dermonecrosis, vascular
CC permeability, edema, inflammatory response, and platelet aggregation
CC (By similarity). {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC ECO:0000250|UniProtKB:P0CE80, ECO:0000269|PubMed:21692149}.
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:24472346};
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 -!- ACTIVITY REGULATION: Catalytic activity and hemolysis are inhibited by
CC divalent ion chelators (1,10-phenanthroline, EDTA, and EGTA).
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:21692149}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:21692149}.
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; GU121905; ADP00408.1; -; mRNA.
DR AlphaFoldDB; E5D3Z8; -.
DR SMR; E5D3Z8; -.
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; Signal; Toxin; Zymogen.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..26
FT /evidence="ECO:0000250"
FT /id="PRO_0000423636"
FT CHAIN 27..311
FT /note="Dermonecrotic toxin"
FT /id="PRO_0000423637"
FT ACT_SITE 38
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 73
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 58
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 60
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 117
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT DISULFID 77..83
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT MUTAGEN 256
FT /note="W->S: Loss of catalytic and hemolytic activities."
FT /evidence="ECO:0000269|PubMed:24472346"
FT MUTAGEN 257
FT /note="S->A: Small decrease in catalytic activity and no
FT change in hemolytic activity."
FT /evidence="ECO:0000269|PubMed:24472346"
FT MUTAGEN 259
FT /note="D->G: Loss of catalytic and hemolytic activities."
FT /evidence="ECO:0000269|PubMed:24472346"
FT MUTAGEN 262
FT /note="S->A: Decrease in catalytic and hemolytic
FT activities."
FT /evidence="ECO:0000269|PubMed:24472346"
FT MUTAGEN 269
FT /note="D->G: Small decrease in catalytic activity and no
FT change in hemolytic activity."
FT /evidence="ECO:0000269|PubMed:24472346"
SQ SEQUENCE 311 AA; 35170 MW; D4A0065FED989387 CRC64;
MYVHLALILG CWTVVLQGAE TDVGERADNR RPIWNLAHMV NAVKQIPTFL DLGANALEAD
VTFKGSVPTY TYHGTPCDFG RDCIRWEYFN VFLKTLREYT TPGNAKYRDG FILFVLDLKT
GSLSNDQVRP AGENVAKELL QNYWNNGNNG GRAYVVLSLP DIGHYEFVRG FKEVLKKEGH
EDLLEKVGYD FSGPYLPSLP TLDATHEAYK KAGVDGHIWL SDGLTNFSPL GDMARLKEAI
KSRDSANGFI NKIYYWSVDK YSTTRTALDV GVDGIMTNYP NVLIDVLNED GYKDNYRLAT
YDDNPWETYK K
