A1LB1_LOXAR
ID A1LB1_LOXAR Reviewed; 309 AA.
AC Q4ZFU2;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Dermonecrotic toxin LarSicTox-alphaIB2bi {ECO:0000303|PubMed:25752604};
DE EC=4.6.1.- {ECO:0000269|PubMed:24009677, ECO:0000269|PubMed:25752604};
DE AltName: Full=Laz-SMase D;
DE AltName: Full=Phospholipase D;
DE Short=PLD;
DE AltName: Full=Sphingomyelin phosphodiesterase D 2;
DE Short=SMD 2;
DE Short=SMase D 2;
DE Short=Sphingomyelinase D 2;
DE Flags: Precursor; Fragment;
OS Loxosceles arizonica (Arizona brown spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Loxosceles.
OX NCBI_TaxID=196454;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=15777950; DOI=10.1016/j.toxicon.2004.11.011;
RA Binford G.J., Cordes M.H.J., Wells M.A.;
RT "Sphingomyelinase D from venoms of Loxosceles spiders: evolutionary
RT insights from cDNA sequences and gene structure.";
RL Toxicon 45:547-560(2005).
RN [2]
RP TOXIC DOSE, AND SUBCELLULAR LOCATION.
RX PubMed=22561243; DOI=10.1016/j.toxicon.2012.04.350;
RA Zobel-Thropp P.A., Kerins A.E., Binford G.J.;
RT "Sphingomyelinase D in sicariid spider venom is a potent insecticidal
RT toxin.";
RL Toxicon 60:265-271(2012).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-74.
RX PubMed=24009677; DOI=10.1371/journal.pone.0072372;
RA Lajoie D.M., Zobel-Thropp P.A., Kumirov V.K., Bandarian V., Binford G.J.,
RA Cordes M.H.;
RT "Phospholipase D toxins of brown spider venom convert
RT lysophosphatidylcholine and sphingomyelin to cyclic phosphates.";
RL PLoS ONE 8:E72372-E72372(2013).
RN [4]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=25752604; DOI=10.1074/jbc.m115.636951;
RA Lajoie D.M., Roberts S.A., Zobel-Thropp P.A., Delahaye J.L., Bandarian V.,
RA Binford G.J., Cordes M.H.;
RT "Variable substrate preference among phospholipase D toxins from Sicariid
RT spiders.";
RL J. Biol. Chem. 290:10994-11007(2015).
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 (PubMed:24009677, PubMed:25752604).
CC This toxin acts on sphingomyelin (SM) with high activity and on
CC lysophosphatidylcholine (LPC) and ceramide phosphoethanolamine (CPE)
CC with low activity (PubMed:24009677, PubMed:25752604). In vivo, shows
CC potent insecticidal activities (PubMed:22561243). On mammals, induces
CC dermonecrosis, hemolysis, increased vascular permeability, edema,
CC inflammatory response, and platelet aggregation (By similarity).
CC {ECO:0000250|UniProtKB:P0CE80, ECO:0000269|PubMed:22561243,
CC ECO:0000269|PubMed:24009677, ECO:0000269|PubMed:25752604}.
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:0000269|PubMed:24009677, ECO:0000269|PubMed:25752604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-hexanoyl-sphing-4-enine-1-phosphocholine = choline + N-
CC (hexanoyl)-sphing-4-enine-1,3-cyclic phosphate; Xref=Rhea:RHEA:60620,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:78254, ChEBI:CHEBI:143883;
CC Evidence={ECO:0000269|PubMed:24009677, ECO:0000269|PubMed:25752604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(dodecanoyl)-sphing-4-enine-1-phosphocholine = choline + N-
CC dodecanoyl-sphing-4-enine-1,3-cyclic phosphate; Xref=Rhea:RHEA:60636,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:137334, ChEBI:CHEBI:143884;
CC Evidence={ECO:0000269|PubMed:25752604};
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:0000269|PubMed:24009677, ECO:0000269|PubMed:25752604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-tetradecanoyl-sn-glycero-3-phosphocholine = 1-tetradecanoyl-
CC sn-glycero-2,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60604,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:64489, ChEBI:CHEBI:143882;
CC Evidence={ECO:0000269|PubMed:25752604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octanoyl-sn-glycero-3-phosphocholine = 1-octanoyl-sn-
CC glycero-2,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60612,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:143866, ChEBI:CHEBI:143876;
CC Evidence={ECO:0000269|PubMed:24009677, ECO:0000269|PubMed:25752604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine = 1-hexadecanoyl-
CC sn-glycero-2,3-cyclic phosphate + choline; Xref=Rhea:RHEA:60656,
CC ChEBI:CHEBI:15354, ChEBI:CHEBI:72998, ChEBI:CHEBI:143893;
CC Evidence={ECO:0000269|PubMed:24009677};
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:0000269|PubMed:25752604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-dodecanoyl-heptadecasphing-4-enine-1-phosphoethanolamine =
CC ethanolamine + N-dodecanoyl-heptadecasphing-4-enine-1,3-cyclic
CC phosphate; Xref=Rhea:RHEA:60616, ChEBI:CHEBI:57603,
CC ChEBI:CHEBI:143864, ChEBI:CHEBI:143865;
CC Evidence={ECO:0000269|PubMed:25752604};
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:22561243}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:22561243}.
CC -!- TOXIC DOSE: PD(50) is 2.27 +-0.43 ug/g when injected into cricket
CC (Acheta domestica) (observed at 60 minutes).
CC {ECO:0000269|PubMed:22561243}.
CC -!- TOXIC DOSE: LD(50) is 2.27 +-0.43 ug/g when injected into cricket
CC (Acheta domestica) (observed at 24 hours).
CC {ECO:0000269|PubMed:22561243}.
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 catalytic 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:0000269|PubMed:24009677,
CC ECO:0000269|PubMed:25752604}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY699703; AAW22997.1; -; mRNA.
DR AlphaFoldDB; Q4ZFU2; -.
DR SMR; Q4ZFU2; -.
DR SwissLipids; SLP:000001960; -.
DR ArachnoServer; AS000135; Sphingomyelinase D (LaSicTox-alphaIB2bi).
DR BRENDA; 3.1.4.41; 8289.
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; Glycoprotein; Hemolysis;
KW Lipid degradation; Lipid metabolism; Lyase; Magnesium; Metal-binding;
KW Secreted; Signal; Toxin; Zymogen.
FT SIGNAL <1..1
FT /evidence="ECO:0000255"
FT PROPEP 2..27
FT /evidence="ECO:0000250"
FT /id="PRO_0000279549"
FT CHAIN 28..309
FT /note="Dermonecrotic toxin LarSicTox-alphaIB2bi"
FT /id="PRO_0000279550"
FT ACT_SITE 38
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 74
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 118
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT CARBOHYD 286
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 78..84
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 80..223
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT MUTAGEN 74
FT /note="H->N: Does not release choline from LPC."
FT /evidence="ECO:0000269|PubMed:24009677"
FT NON_TER 1
SQ SEQUENCE 309 AA; 35179 MW; 3BBB88FA597C7605 CRC64;
VRATEKFAPI YFFCHPLQSA ETDVAERANK RPIWIMGHMV NANYQIDEFV NLGANSIETD
VSFDSSANPE YTYHGVPCDC RRWCKKWEYF NNFLKALRKA TTPGDSKYHE KLVLVVFDLK
TGSLYDNQAY DAGKKLAKNL LQHYWNNGNN GGRAYIVLSI PNLAHYKLIT GFKETLKTEG
HPELMEKVGY DFSGNDNIDQ VANAYKKAGV TGHVWQSDGI TNCVASFIRG LDRAKKAVKN
RDSSNGYINK VYYWTVDKYA TTREAFDIGV DGIMTNYPDV IANVLNESAY KGKFRLATYD
DNPWETFKN
