B1H_LOXLA
ID B1H_LOXLA Reviewed; 304 AA.
AC Q8I912;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Dermonecrotic toxin LlSicTox-betaIA1;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=LlH10;
DE Short=H10 {ECO:0000303|PubMed:19249326};
DE AltName: Full=Phospholipase D;
DE Short=PLD;
DE AltName: Full=SMase II {ECO:0000303|PubMed:19249326};
DE AltName: Full=Sphingomyelin phosphodiesterase D;
DE Short=SMD;
DE Short=SMase D;
DE Short=Sphingomyelinase D;
DE Flags: Precursor;
OS Loxosceles laeta (South American recluse spider) (Scytodes laeta).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Loxosceles.
OX NCBI_TaxID=58217;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=12419302; DOI=10.1016/s0006-291x(02)02521-4;
RA Fernandes-Pedrosa M.F., Junqueira de Azevedo I.L.M.,
RA Goncalves-de-Andrade R.M., van den Berg C.W., Ramos C.R.R., Ho P.L.,
RA Tambourgi D.V.;
RT "Molecular cloning and expression of a functional dermonecrotic and
RT haemolytic factor from Loxosceles laeta venom.";
RL Biochem. Biophys. Res. Commun. 298:638-645(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, 3D-STRUCTURE MODELING, AND CATALYTIC
RP ACTIVITY.
RX PubMed=19249326; DOI=10.1016/j.toxicon.2009.02.013;
RA de Santi Ferrara G.I., Fernandes-Pedrosa Mde F.,
RA Junqueira de Azevedo I.L.M., Goncalves-de-Andrade R.M., Portaro F.C.,
RA Manzoni-de-Almeida D., Murakami M.T., Arni R.K., van den Berg C.W.,
RA Ho P.L., Tambourgi D.V.;
RT "SMase II, a new sphingomyelinase D from Loxosceles laeta venom gland:
RT molecular cloning, expression, function and structural analysis.";
RL Toxicon 53:743-753(2009).
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) with low activity (PubMed:19249326). It may also act
CC on ceramide phosphoethanolamine (CPE), lysophosphatidylcholine (LPC)
CC and lysophosphatidylethanolamine (LPE), but not on
CC lysophosphatidylserine (LPS), and lysophosphatidylglycerol (LPG) (By
CC similarity). It acts by transphosphatidylation, releasing exclusively
CC cyclic phosphate products as second products (By similarity). Induces
CC hemolysis, dermonecrosis, and edema (PubMed:19249326). Also induces
CC platelet aggregation (By similarity).
CC {ECO:0000250|UniProtKB:A0A0D4WTV1, ECO:0000250|UniProtKB:P0CE80,
CC ECO:0000269|PubMed:19249326}.
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:0000305|PubMed:19249326};
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|PubMed:12419302}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:12419302}.
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; AY093601; AAM21156.1; -; mRNA.
DR AlphaFoldDB; Q8I912; -.
DR SMR; Q8I912; -.
DR ArachnoServer; AS000126; Sphingomyelinase D (LlSicTox-betaIA1).
DR BRENDA; 3.1.4.41; 6922.
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; Hemolysis;
KW Hemostasis impairing toxin; Lipid degradation; Lipid metabolism; Lyase;
KW Magnesium; Metal-binding; Platelet aggregation activating toxin; Secreted;
KW Signal; Toxin; Zymogen.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..26
FT /evidence="ECO:0000250"
FT /id="PRO_0000279574"
FT CHAIN 27..304
FT /note="Dermonecrotic toxin LlSicTox-betaIA1"
FT /id="PRO_0000279575"
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 DISULFID 78..84
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 80..223
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT CONFLICT 205
FT /note="Y -> I (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 304 AA; 34519 MW; 3CAFEBA6C3521BE8 CRC64;
MLLSAVISFI GFAAFLQEAN GHVVERADSR KPIWDIAHMV NDLDLVDEYL GDGANALEAD
LAFTSDGTAD EMYHGVPCDC FRSCTRSEKF STYMDYIRRI TTPGSSNFRP QMLLLIIDLK
LKGIEPNVAY AAGKSTAKKL LSSYWQDGKS GARAYIVLSL ETITRQDFIS GFKDAIDASG
HTELYEKIGW DFSGNEDLGE IRRIYQKYGI DDHIWQGDGI TNCWVRDDDR LKEAIKKKND
PNYKYTKKVY TWSIDKNASI RNALRLGVDA IMTNYPEDVK DILQESEFSG YLRMATYDDN
PWVK
