BX17_LOXGA
ID BX17_LOXGA Reviewed; 36 AA.
AC P0C2K3;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 25-MAY-2022, entry version 39.
DE RecName: Full=Dermonecrotic toxin LgSicTox-beta-LOXN1/LOXN7;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
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: Fragments;
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 PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=15852345; DOI=10.1002/pmic.200401096;
RA Machado L.F., Laugesen S., Botelho E.D., Ricart C.A.O., Fontes W.,
RA Barbaro K.C., Roepstorff P., Sousa M.V.;
RT "Proteome analysis of brown spider venom: identification of loxnecrogin
RT isoforms in Loxosceles gaucho venom.";
RL Proteomics 5:2167-2176(2005).
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:0000269|PubMed:15852345}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:15852345}.
CC -!- PTM: Contains 2 disulfide bonds. {ECO:0000250}.
CC -!- MISCELLANEOUS: LOXN1 (pI=4.41) and LOXN7 (pI=6.38) are not the same
CC protein, but the partial sequence of LOXN7 (AA 1-9) is identical to the
CC sequence of LOXN1.
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}.
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DR AlphaFoldDB; P0C2K3; -.
DR ArachnoServer; AS000147; Sphingomyelinase D (LOXN1) (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: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.
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..>36
FT /note="Dermonecrotic toxin LgSicTox-beta-LOXN1/LOXN7"
FT /id="PRO_0000279560"
FT NON_CONS 10..11
FT /evidence="ECO:0000305"
FT NON_CONS 21..22
FT /evidence="ECO:0000305"
FT NON_TER 36
SQ SEQUENCE 36 AA; 4156 MW; E9E0E13D2EA5957F CRC64;
ADNRRPIWVM LLSSYWQDGN SLGVDAIMTN YPEDVK
