A1H_LOXGA
ID A1H_LOXGA Reviewed; 280 AA.
AC Q4VDB5;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Dermonecrotic toxin LgSicTox-alphaIA1;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
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 gaucho (Spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Loxosceles.
OX NCBI_TaxID=58216;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Venom gland;
RA Silvestre F.G., Castro C.S., Chavez-Olortegui C., Kalapothakis E.;
RT "Molecular cloning of a protein from the dermonecrotic family of Loxosceles
RT gaucho spider venom.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
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|Ref.1}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.1}.
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; AY974250; AAY42401.1; -; Genomic_DNA.
DR AlphaFoldDB; Q4VDB5; -.
DR SMR; Q4VDB5; -.
DR ArachnoServer; AS000130; Sphingomyelinase D (LgSicTox-alphaIA1).
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 3: Inferred from homology;
KW Cytolysis; Dermonecrotic toxin; Disulfide bond; Hemolysis;
KW Lipid degradation; Lipid metabolism; Lyase; Magnesium; Metal-binding;
KW Secreted; Toxin.
FT CHAIN 1..280
FT /note="Dermonecrotic toxin LgSicTox-alphaIA1"
FT /id="PRO_0000279558"
FT ACT_SITE 12
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 48
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 32
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 92
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT DISULFID 52..58
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
SQ SEQUENCE 280 AA; 31282 MW; 40E4A1F6155FA9CE CRC64;
AGNRRPIWIM GHMVNAIGQI DEFVNLGANS IETDVSFDDN ANPEYTYHGI PCDSGRNCKK
YENFNDFLKG LRSATTPGNS KYQEKLVLVV FDLKTGSLYD NQANDAGKKW AKNLLQHYWN
NGNNGGRAYI VLSIPDLNHY PLIKGFKDQL TKDGHPELMD KVGHDFSGND DISDVGKAYK
KAGITGHIWQ SDGITNSLPR GLSRVNAAVA NRDSANGFIN KVYYWTVDKR STTRDALDAG
VDGIMTNYPD VITDVLNEAA YKKKFRVATY DDNPWVTFNK
