A1IA3_LOXIN
ID A1IA3_LOXIN Reviewed; 305 AA.
AC B2KKV8;
DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Dermonecrotic toxin LiSicTox-alphaIA2aiii;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=Loxtox i3;
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 intermedia (Brown spider).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Araneae;
OC Araneomorphae; Haplogynae; Scytodoidea; Sicariidae; Loxosceles.
OX NCBI_TaxID=58218;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=17825864; DOI=10.1016/j.toxicon.2007.07.001;
RA Kalapothakis E., Chatzaki M., Goncalves-Dornelas H., de Castro C.S.,
RA Silvestre F.G., Laborne F.V., de Moura J.F., Veiga S.S.,
RA Chavez-Olortegui C., Granier C., Barbaro K.C.;
RT "The Loxtox protein family in Loxosceles intermedia (Mello-Leitao) venom.";
RL Toxicon 50:938-946(2007).
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:17825864}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:17825864}.
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; EF535252; ABU43331.1; -; mRNA.
DR AlphaFoldDB; B2KKV8; -.
DR SMR; B2KKV8; -.
DR ArachnoServer; AS000490; Sphingomyelinase D (LiSicTox-alphaIA2aiii).
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..17
FT /evidence="ECO:0000255"
FT PROPEP 18..25
FT /evidence="ECO:0000250"
FT /id="PRO_0000380637"
FT CHAIN 26..305
FT /note="Dermonecrotic toxin LiSicTox-alphaIA2aiii"
FT /id="PRO_0000380638"
FT ACT_SITE 37
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 73
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 57
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 59
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 117
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT CARBOHYD 282
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 77..83
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 79..222
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT NON_TER 1
SQ SEQUENCE 305 AA; 34105 MW; 6F22905D38BACAF6 CRC64;
LPYIALILVC WSVLSQAAQT DVEERADKRR PIWIMGHMVN AIAQIDEFVN LGANSIETDV
SFDDNANPEY TYHGIPCDCG RSCLKWENFN DFLKGLRSAT TPGNAKYQAK LILVVFDLKT
GSLYDNQANE AGKKLAKNLL KHYWNNGNNG GRAYIVLSIP DLNHYPLIKG FKDQLTQDGH
PELMDKVGHD FSGNDAIGDV GNAYKKAGIS GHVWQSDGIT NCLLRGLDRV KQAIANRDSA
KGFINKVYYW TVDKRATTRD ALDAGVDGVM TNYPDVITDV LNESAYKNKF RVASYEDNPW
ETFKK
