B1O_SICTE
ID B1O_SICTE Reviewed; 272 AA.
AC C0JB39;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 1.
DT 03-AUG-2022, entry version 35.
DE RecName: Full=Dermonecrotic toxin StSicTox-betaIC1 {ECO:0000303|PubMed:19042943};
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: Fragment;
OS Sicarius terrosus (Cave spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Sicarius.
OX NCBI_TaxID=571544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND NOMENCLATURE.
RC TISSUE=Venom gland;
RX PubMed=19042943; DOI=10.1093/molbev/msn274;
RA Binford G.J., Bodner M.R., Cordes M.H., Baldwin K.L., Rynerson M.R.,
RA Burns S.N., Zobel-Thropp P.A.;
RT "Molecular evolution, functional variation, and proposed nomenclature of
RT the gene family that includes sphingomyelinase D in sicariid spider
RT venoms.";
RL Mol. Biol. Evol. 26:547-566(2009).
RN [2]
RP IMPORTANT SITES FOR ACTIVITY ON SPHINGOMYELIN.
RX PubMed=16480957; DOI=10.1016/j.bbrc.2006.01.123;
RA Murakami M.T., Fernandes-Pedrosa M.F., de Andrade S.A., Gabdoulkhakov A.,
RA Betzel C., Tambourgi D.V., Arni R.K.;
RT "Structural insights into the catalytic mechanism of sphingomyelinases D
RT and evolutionary relationship to glycerophosphodiester
RT phosphodiesterases.";
RL Biochem. Biophys. Res. Commun. 342:323-329(2006).
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. This toxin acts on
CC lysophosphatidylethanolamine (LPE) and ceramide phosphoethanolamine
CC (CPE) with high activity. This toxin acts on sphingomyelin (SM) with
CC very low activity and is not active on lysophosphatidylserine (LPS),
CC lysophosphatidylcholine (LPC) and lysophosphatidylglycerol (LPG). It
CC acts by transphosphatidylation, releasing exclusively cyclic phosphate
CC as second products. It is not surprising that spider toxins have
CC affinity for ethanolamine-containing sphingolipids since they are
CC common in insect prey (By similarity). Induces dermonecrosis,
CC hemolysis, increased vascular permeability, edema, inflammatory
CC response, and platelet aggregation (By similarity).
CC {ECO:0000250|UniProtKB:A0A0D4WV12, 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:A0A0D4WV12};
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:0000250|UniProtKB:A0A0D4WV12};
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:A0A0D4WV12};
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:0000250|UniProtKB:A0A0D4WV12};
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:A0A0D4WV12};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-tetradecanoyl-sn-glycero-3-phosphoethanolamine = 1-
CC tetradecanoyl-sn-glycero-2,3-cyclic phosphate + ethanolamine;
CC Xref=Rhea:RHEA:60608, ChEBI:CHEBI:57603, ChEBI:CHEBI:84299,
CC ChEBI:CHEBI:143882; Evidence={ECO:0000250|UniProtKB:A0A0D4WV12};
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:19042943}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:19042943}.
CC -!- SIMILARITY: Belongs to the arthropod phospholipase D family. Class II
CC subfamily. Class IIb sub-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; FJ171474; ACN48970.1; -; mRNA.
DR AlphaFoldDB; C0JB39; -.
DR SMR; C0JB39; -.
DR PRIDE; C0JB39; -.
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; Toxin.
FT CHAIN <1..272
FT /note="Dermonecrotic toxin StSicTox-betaIC1"
FT /id="PRO_0000392855"
FT ACT_SITE 5
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 41
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 25
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 27
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 85
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT SITE 89
FT /note="May prevent sphingomyelin recognition"
FT /evidence="ECO:0000305|PubMed:16480957"
FT SITE 128
FT /note="May prevent sphingomyelin recognition"
FT /evidence="ECO:0000305|PubMed:16480957"
FT DISULFID 45..51
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 47..191
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT NON_TER 1
SQ SEQUENCE 272 AA; 31062 MW; 0F2A852AF825481C CRC64;
WIMGHMVNDL DLVDEYLDDG ANSLELDVEF SKSGTALRTY HGVPCDCFRS CTRSEKFSKY
LDYIRQLTTP GNSKFRSRLI LLVLDLKLNP LSSSAAYNAG ADVARNLLDN YWQRGESKAR
AYIVLSLETI AGAEFITGFK DIMKKEGFDE KYYDKIGWDF SGNEDLGKIR DVLESHGIRE
HIWQGDGITN CLPRDDNRLK QAISRRYSPT YVYADKVYTW SIDKESSIEN ALRLGVDGVM
TNYPARVISV LGEREFSGKL RLATYDDNPW EK
