A1H1_LOXRE
ID A1H1_LOXRE Reviewed; 279 AA.
AC P0CE78; Q5I225; Q5YD74;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Dermonecrotic toxin LrSicTox-alphaIA1i;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Lr2 {ECO:0000303|PubMed:15450925};
DE AltName: Full=Phospholipase D;
DE Short=PLD;
DE AltName: Full=SMaseD/LysoPLD;
DE AltName: Full=Sphingomyelin phosphodiesterase D 2;
DE Short=SMD 2;
DE Short=SMase D 2;
DE Short=Sphingomyelinase D 2;
OS Loxosceles reclusa (Brown recluse spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Loxosceles.
OX NCBI_TaxID=6921;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
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) (By similarity). It also acts on a broad range of
CC lysophospholipids, like lysophosphatidylinositol (LPI),
CC lysophosphatidylglycerol (LPG), lysophosphatidylethanolamine (LPE),
CC lysobisphosphatidic acid (LBPA), lysophosphatidylserine (LPS) and
CC lysophosphatidylcholines (LPC) of varying chain lengths (By
CC similarity). The substrate preference is LPI > LPG > LPS > LPC >> LPE,
CC LBPA (By similarity). Furthermore, the enzyme also act on cyclic
CC phosphatidic acid and lyso-platelet activating factor (LPAF, an alkyl-
CC LPC) (By similarity). The enzyme does not act on
CC sphingosylphosphorylcholine (SPC, also known as lyso-sphingomyelin) and
CC PAF (By similarity). The toxin may also act on ceramide
CC phosphoethanolamine (CPE) (By similarity). It acts by
CC transphosphatidylation, releasing exclusively cyclic phosphate products
CC as second products (By similarity). It does not exhibit detectable
CC PLA1/2 activity (By similarity). It induces dose-dependent hemolysis
CC and dermonecrosis (By similarity). Also induces increased vascular
CC permeability, edema, inflammatory response, and platelet aggregation
CC (By similarity). {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC ECO:0000250|UniProtKB:P0CE79, 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 -!- ACTIVITY REGULATION: Inhibited with low affinity by edelfosine.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:15450925}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:15450925}.
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 EMBL; AY559847; AAT66076.1; -; mRNA.
DR AlphaFoldDB; P0CE78; -.
DR SMR; P0CE78; -.
DR BRENDA; 3.1.4.41; 3077.
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; Glycoprotein; Hemolysis;
KW Lipid degradation; Lipid metabolism; Lyase; Magnesium; Metal-binding;
KW Secreted; Toxin.
FT CHAIN 1..279
FT /note="Dermonecrotic toxin LrSicTox-alphaIA1i"
FT /id="PRO_0000392730"
FT ACT_SITE 11
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 47
FT /note="Nucleophile"
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 BINDING 91
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 51..57
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 53..196
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
SQ SEQUENCE 279 AA; 31274 MW; 40B3FAE6A57B4B7C CRC64;
ANKRPAWIMG HMVNAIYQID EFVNLGANSI ETDVSFDKDA NPEYTYHGVP CDCGRSCLKW
EYFSDFLKGL RKATTPGDSK YHAKLVLVVF DLKTGSLYDN QAYDAGKKLA KNLLKHYWNN
GNNGGRAYIV LSIPDLNHYK LITGFKETLK SEGHPELMDK VGHDFSGNDA IGDVGNAYKK
AGVTGHVWQS DGITNCLLRG LSRVKDAVKN RDSSNGFINK VYYWTVDKRA TTREALDAGV
DGVMTNYPDV ITDVLNESAY KAKFRIATYD DNPWETFKN
