A1LA_LOXAR
ID A1LA_LOXAR Reviewed; 320 AA.
AC Q7Z1Y7; Q7Z1N1; Q7Z1N2;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Dermonecrotic toxin LarSicTox-alphaIB2a;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Phospholipase D;
DE Short=PLD;
DE AltName: Full=Sphingomyelin phosphodiesterase D 1;
DE Short=SMD 1;
DE Short=SMase D 1;
DE Short=Sphingomyelinase D 1;
DE Flags: Precursor;
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 [GENOMIC DNA] OF 1-117 AND 279-320, AND NUCLEOTIDE
RP SEQUENCE [MRNA] OF 55-320.
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).
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 may also act on ceramide
CC phosphoethanolamine (CPE), lysophosphatidylcholine (LPC) and
CC lysophosphatidylethanolamine (LPE), but not on lysophosphatidylserine
CC (LPS), and lysophosphatidylglycerol (LPG) (By similarity). It acts by
CC transphosphatidylation, releasing exclusively cyclic phosphate products
CC as second products (By similarity). Induces dermonecrosis, hemolysis,
CC increased vascular permeability, edema, inflammatory response, and
CC platelet aggregation (By similarity).
CC {ECO:0000250|UniProtKB:A0A0D4WTV1, 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 -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:15777950}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:15777950}.
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; AF512953; AAP44735.2; -; mRNA.
DR EMBL; AF512954; AAP46535.1; -; Genomic_DNA.
DR EMBL; AF512955; AAP46536.1; -; Genomic_DNA.
DR AlphaFoldDB; Q7Z1Y7; -.
DR SMR; Q7Z1Y7; -.
DR ArachnoServer; AS000128; Sphingomyelinase D (LaSicTox-alphaIB2a).
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 2: Evidence at transcript 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..15
FT /evidence="ECO:0000255"
FT PROPEP 16..41
FT /evidence="ECO:0000250"
FT /id="PRO_0000035577"
FT CHAIN 42..320
FT /note="Dermonecrotic toxin LarSicTox-alphaIB2a"
FT /id="PRO_0000035578"
FT ACT_SITE 52
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 88
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 72
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 74
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 132
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 92..98
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 94..237
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT CONFLICT 96
FT /note="G -> R (in Ref. 1; AAP46535)"
FT /evidence="ECO:0000305"
FT CONFLICT 286
FT /note="P -> T (in Ref. 1; AAP46536)"
FT /evidence="ECO:0000305"
FT CONFLICT 296
FT /note="P -> L (in Ref. 1; AAP46536)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 320 AA; 36153 MW; 280D71E865D19DAA CRC64;
MSHSSTALLH PYVAARATEK FAPIYFFCHP LQSAETDVAE RANKRPIWIM GHMVNANYQI
DEFVNLGANS IETDVSFDSS ANPEYTYHGV PCDCRGWCKK WEYFNNFLKA LRKATTPGDS
KYHEKLVLVV FDLKTGSLYD NQAYDAGKKL AKNLLQHYWN NGNNGGRAYI VLSIPNLAHY
KLITGFKETL KTEGHPELME KVGYDFSGND NIDQVANAYK KAGVTGHVWQ SDGITNCLLR
GLDRVRKAVA NRDSSNGYIN KVYYWTVDKR QSTKNALDAG VDGIMPNYPD VIADVPNESA
YKAKFRIASY DDNPWETFKN
