A331_LOXLA
ID A331_LOXLA Reviewed; 311 AA.
AC Q8I913;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Dermonecrotic toxin LlSicTox-alphaIII3i;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=LlH13;
DE AltName: Full=Phospholipase D;
DE Short=PLD;
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].
RC TISSUE=Venom gland;
RX PubMed=12419302; DOI=10.1016/s0006-291x(02)02521-4;
RA Fernandes-Pedrosa M.F., Junqueira de Azevedo I.L.M.,
RA Goncalves-de-Andrade R.M., van den Berg C.W., Ramos C.R.R., Ho P.L.,
RA Tambourgi D.V.;
RT "Molecular cloning and expression of a functional dermonecrotic and
RT haemolytic factor from Loxosceles laeta venom.";
RL Biochem. Biophys. Res. Commun. 298:638-645(2002).
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) (By similarity). 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).
CC {ECO:0000250|UniProtKB:A0A0D4WTV1, ECO:0000250|UniProtKB:P0CE80}.
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:0000250|UniProtKB:A0A0D4WTV1};
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:12419302}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:12419302}.
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; AY093600; AAM21155.1; -; mRNA.
DR AlphaFoldDB; Q8I913; -.
DR SMR; Q8I913; -.
DR ArachnoServer; AS000127; Sphingomyelinase D (LlSicTox-alphaIII3i).
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 2: Evidence at transcript 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_0000279576"
FT CHAIN 27..311
FT /note="Dermonecrotic toxin LlSicTox-alphaIII3i"
FT /id="PRO_0000279577"
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"
SQ SEQUENCE 311 AA; 35451 MW; 39040EB3A21F56E1 CRC64;
MYVHLALILG CWTVILQGAE TDVGERADKR RPIWNLGHMV NAVKQIPTFL NDGANAIEAD
ITFKGAVPTY SYHGTPCDFG RDCIRWEYFD VFLQTLRDYT TPGNSKYYEK FILFVLDLKT
GSLNNNEVRK AGENIAKGLL KNYWNNGNNG GRAYVVLSLP DIAHYEFIRR FKEVLKAEGH
ENLLDKVGYD LSGPYLPSLP SLDSVHEAFR KAGVDGHVWL SDGLTNWAPL GDMARLKEIV
ERRDSENGFI SKVYYWSVDK YSTTRTALDV GVDGIMTNFP YVIIDVLNEN GYKDKYRLAT
YDDNPWETFK K
