B1D1_LOXAR
ID B1D1_LOXAR Reviewed; 289 AA.
AC A0A0D4WTV1;
DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2015, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Dermonecrotic toxin LarSicTox-betaID1 {ECO:0000303|PubMed:25752604};
DE EC=4.6.1.- {ECO:0000269|PubMed:25752604};
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: 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], CATALYTIC ACTIVITY, AND FUNCTION.
RC TISSUE=Venom gland;
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:25752604). This toxin acts on
CC sphingomyelin (SM) and on ceramide phosphoethanolamine (CPE) with high
CC activity (PubMed:25752604). It also acts on lysophosphatidylcholine
CC (LPC) and on lysophosphatidylethanolamine (LPE) with moderate activity
CC (PubMed:25752604). It is not active on lysophosphatidylserine (LPS),
CC and lysophosphatidylglycerol (LPG) (PubMed:25752604). It acts by
CC transphosphatidylation, releasing exclusively cyclic phosphate as
CC second products (PubMed:25752604). It is not surprising that spider
CC toxins have affinity for ethanolamine-containing sphingolipids since
CC they are common in insect prey (PubMed:25752604). 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: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: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: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=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 -!- 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: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:25752604};
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:0000269|PubMed:25752604};
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: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:0000305|PubMed:25752604}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:25752604}.
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:Q4ZFU2,
CC ECO:0000269|PubMed:25752604}.
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DR EMBL; KM884812; AJV88487.1; -; mRNA.
DR AlphaFoldDB; A0A0D4WTV1; -.
DR SMR; A0A0D4WTV1; -.
DR SwissLipids; SLP:000001961; -.
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 Lipid degradation; Lipid metabolism; Lyase; Magnesium; Metal-binding;
KW Secreted; Signal; Toxin; Zymogen.
FT SIGNAL <1..2
FT /evidence="ECO:0000305"
FT PROPEP 3..11
FT /evidence="ECO:0000250|UniProtKB:K9USW8"
FT /id="PRO_0000447763"
FT CHAIN 11..289
FT /note="Dermonecrotic toxin LarSicTox-betaID1"
FT /id="PRO_0000447764"
FT ACT_SITE 22
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 58
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 42
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 44
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 102
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT DISULFID 62..68
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 64..207
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT NON_TER 1
FT /evidence="ECO:0000305|PubMed:25752604"
SQ SEQUENCE 289 AA; 33102 MW; CAB178550D76C954 CRC64;
EGAEQDGSER TDGGRPIWNI AHMVNNKQAI DKYLDKGANS VESDVSFDSD GKPEKMLHGI
PCDCGRKCLN QMSFTDYLDY MRQLTTPGDP KFRENLILIM LDLKLKSVAA NLAYSSGQEV
ALQMLNTYWK RGESGARAYI VLSIPTIKRV TFVRGFYDKL HSEGFDQYRE KVGVDFSGNE
DLDETGRILS SQNILDHIWQ SDGITNCIFR VMTRLKKAIN KRDSNGYMVK VYYWSVDKYT
IMRKTLRAGA DGMITNFPDR LVSVLNEREF SGKFRLATYD DNPWERYKA
