A1IA1_LOXIN
ID A1IA1_LOXIN Reviewed; 306 AA.
AC P0CE83; P83046; Q2XQV2; Q6W8Q4;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 1.
DT 03-AUG-2022, entry version 35.
DE RecName: Full=Dermonecrotic toxin LiSicTox-alphaIA2ai;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=LiP2;
DE Short=P2 {ECO:0000303|PubMed:9790962};
DE AltName: Full=Phospholipase D;
DE Short=PLD;
DE AltName: Full=Sphingomyelin phosphodiesterase D 2;
DE Short=SMD 2;
DE Short=SMase D 2;
DE Short=Sphingomyelinase D 2;
DE Flags: Precursor;
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], FUNCTION, CATALYTIC ACTIVITY, AND BIOASSAY.
RC TISSUE=Venom gland;
RX PubMed=15234562; DOI=10.1016/j.molimm.2004.03.027;
RA Tambourgi D.V., Fernandes-Pedrosa M.F., Van Den Berg C.W.,
RA Goncalves-de-Andrade R.M., Ferracini M., Paixao-Cavalcante D., Morgan B.P.,
RA Rushmere N.K.;
RT "Molecular cloning, expression, function and immunoreactivities of members
RT of a gene family of sphingomyelinases from Loxosceles venom glands.";
RL Mol. Immunol. 41:831-840(2004).
RN [2]
RP PROTEIN SEQUENCE OF 27-55, FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom;
RX PubMed=9790962; DOI=10.1006/bbrc.1998.9474;
RA Tambourgi D.V., Magnoli F.C., van den Berg C.W., Morgan B.P.,
RA de Araujo P.S., Alves E.W., Da Silva W.D.;
RT "Sphingomyelinases in the venom of the spider Loxosceles intermedia are
RT responsible for both dermonecrosis and complement-dependent hemolysis.";
RL Biochem. Biophys. Res. Commun. 251:366-373(1998).
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) (PubMed:15234562, PubMed:9790962). 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). It
CC induces complement-dependent hemolysis, dermonecrosis, vascular
CC permeability and platelet aggregation (PubMed:15234562,
CC PubMed:9790962). {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC ECO:0000269|PubMed:9790962}.
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:9790962};
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:9790962}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:9790962}.
CC -!- SIMILARITY: Belongs to the arthropod phospholipase D family. Class II
CC subfamily. Class IIa 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP97092.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY304472; AAP97092.2; ALT_INIT; mRNA.
DR AlphaFoldDB; P0CE83; -.
DR SMR; P0CE83; -.
DR BRENDA; 3.1.4.4; 8287.
DR BRENDA; 3.1.4.41; 8287.
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; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hemolysis; Lipid degradation; Lipid metabolism; Lyase;
KW Magnesium; Metal-binding; Secreted; Signal; Toxin; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..26
FT /evidence="ECO:0000269|PubMed:9790962"
FT /id="PRO_0000035581"
FT CHAIN 27..306
FT /note="Dermonecrotic toxin LiSicTox-alphaIA2ai"
FT /id="PRO_0000035582"
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 CARBOHYD 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 78..84
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 80..223
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
SQ SEQUENCE 306 AA; 34138 MW; 3AB8438788595C46 CRC64;
MLPYIALILV CWSVLSQAAQ TDVEGRADKR RPIWIMGHMV NAIAQIDEFV NLGANSIETD
VSFDDNANPE YTYHGIPCDC GRSCLKWENF NDFLKGLRSA TTPGNAKYQA KLILVVFDLK
TGSLYDNQAN EAGKKLAKNL LKHYWNNGNN GGRAYIVLSI PDLNHYPLIK GFKDQLTQDG
HPELMDKVGH DFSGNDAIGD VGNAYKKAGI SGHVWQSDGI TNCLLRGLDR VKQATANRDS
ANGFINKVYY WTVDKRATTR DALDAGVDGV MTNYPDVITD VLNESAYKNK FRVASYEDNP
WETFKK
