A1O_LOXGA
ID A1O_LOXGA Reviewed; 280 AA.
AC K9USW8;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 1.
DT 03-AUG-2022, entry version 28.
DE RecName: Full=Dermonecrotic toxin LgSicTox-alphaIC1 {ECO:0000303|PubMed:25752604};
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Phospholipase D;
DE Short=PLD;
DE AltName: Full=Phospholipase D LgRec1 {ECO:0000303|PubMed:23770445};
DE AltName: Full=Sphingomyelin phosphodiesterase D;
DE Short=SMD;
DE Short=SMase D;
DE Short=Sphingomyelinase D;
DE Contains:
DE RecName: Full=U1-sicaritoxin-Lg1a {ECO:0000305|PubMed:30563217};
DE Short=U1-SCRTX-Lg1a {ECO:0000303|PubMed:30563217};
DE AltName: Full=Anionic antimicrobial peptide {ECO:0000303|PubMed:30563217};
DE Short=AAMP {ECO:0000303|PubMed:30563217};
DE AltName: Full=Lg-AMP1 {ECO:0000303|PubMed:30563217};
OS Loxosceles gaucho (Spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Loxosceles.
OX NCBI_TaxID=58216;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Venom gland;
RX PubMed=23770445; DOI=10.1016/j.biochi.2013.06.002;
RA Magalhaes G.S., Caporrino M.C., Della-Casa M.S., Kimura L.F.,
RA Prezotto-Neto J.P., Fukuda D.A., Portes-Junior J.A., Neves-Ferreira A.G.,
RA Santoro M.L., Barbaro K.C.;
RT "Cloning, expression and characterization of a phospholipase D from
RT Loxosceles gaucho venom gland.";
RL Biochimie 95:1773-1783(2013).
RN [2]
RP PROTEIN SEQUENCE OF 162-177, FUNCTION, MASS SPECTROMETRY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom;
RX PubMed=30563217; DOI=10.3390/toxins10120522;
RA Segura-Ramirez P.J., Silva Junior P.I.;
RT "Loxosceles gaucho spider venom: an untapped source of antimicrobial
RT agents.";
RL Toxins 10:1-19(2018).
RN [3]
RP NOMENCLATURE.
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 toxin LgSicTox-alphaIC1]: Dermonecrotic toxins
CC cleave the phosphodiester linkage between the phosphate and headgroup
CC of certain phospholipids (sphingolipid and lysolipid substrates),
CC forming an alcohol (often choline) and a cyclic phosphate (By
CC similarity). This toxin acts on sphingomyelin (SM) with high activity
CC (PubMed:23770445). It may also act on ceramide phosphoethanolamine
CC (CPE), lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine
CC (LPE), but not on lysophosphatidylserine (LPS), and
CC lysophosphatidylglycerol (LPG) (By similarity). It acts by
CC transphosphatidylation, releasing exclusively cyclic phosphate products
CC as second products (By similarity). Induces platelet aggregation in
CC platelet rich plasma, but not in washed platelet, indicating that this
CC activity is dependent on plasma components (PubMed:23770445). Also
CC induces hemolysis (PubMed:23770445). In vivo, the recombinant protein
CC evokes an intense inflammatory reaction and dermonecrosis, similar to
CC those induced by L.gaucho total venom (PubMed:23770445). Is a good
CC immunogen, capable of inducing immunoprotection in test animals
CC (PubMed:23770445). {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC ECO:0000269|PubMed:23770445}.
CC -!- FUNCTION: [U1-sicaritoxin-Lg1a]: Anionic antimicrobial peptide that
CC shows antimicrobial activity against Gram-negative bacteria (MIC=1.15-
CC 4.6 uM) (tested on E.coli, P.aeruginosa, and E.cloacae), but not on
CC Gram-negative bacteria (M.luteus, S.aureus, and B.subtilis), neither on
CC fungi and yeasts (A.niger, C.albicans and C.krusei). Does not show
CC hemolytic effects against human erythrocytes, and has no cytotoxic
CC effects against human cervical carcinoma cells (HeLa).
CC {ECO:0000269|PubMed:30563217}.
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:23770445};
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:0000269|PubMed:30563217}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:23770445, ECO:0000305|PubMed:30563217}.
CC -!- MASS SPECTROMETRY: [U1-sicaritoxin-Lg1a]: Mass=1695.75;
CC Method=Electrospray; Note=Monoisotopic mass.;
CC Evidence={ECO:0000269|PubMed:30563217};
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; JX866729; AFY98967.1; -; mRNA.
DR AlphaFoldDB; K9USW8; -.
DR SMR; K9USW8; -.
DR BRENDA; 3.1.4.41; 10588.
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:0042742; P:defense response to bacterium; 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 Antibiotic; Antimicrobial; Cytolysis; Dermonecrotic toxin;
KW Direct protein sequencing; Disulfide bond; Hemolysis; Lipid degradation;
KW Lipid metabolism; Lyase; Magnesium; Metal-binding; Secreted; Toxin.
FT CHAIN 1..280
FT /note="Dermonecrotic toxin LgSicTox-alphaIC1"
FT /id="PRO_0000423639"
FT PEPTIDE 162..177
FT /note="U1-sicaritoxin-Lg1a"
FT /evidence="ECO:0000269|PubMed:30563217"
FT /id="PRO_0000448551"
FT ACT_SITE 12
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 48
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 32
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 92
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT DISULFID 52..58
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 54..197
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
SQ SEQUENCE 280 AA; 31447 MW; E853856FC9C37785 CRC64;
ADNRRPIWVM GHMVNSLAQI DEFVGLGSNS IETDVSFDKQ ANPEYTYHGI PCDCGRACLH
STKFNDFLKG LRKVTTPGDS KYLEKLILVV FDLKTGSLYD NQAYDAGTKL AKNLLQHYWN
NGNNGGRAYI ILSIPNLNHY KLITGFKETL KNEGHEELLE KVGTDFSGND DISDVQKTYN
KAGVTGHVWQ SDGITNCLLR GLTRVKAAVA NRDSGSGIIN KVYYWTVDKR QSTRDTLDAN
VDGIMTNYPD ITVEILNEAA YKKKFRIATY EDNPWETFKG
