A1HB1_LOXIN
ID A1HB1_LOXIN Reviewed; 306 AA.
AC P0CE81; B2KKV9; P83045; Q3HL91; Q6W8Q5; Q7YW73;
DT 23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 1.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=Dermonecrotic toxin LiSicTox-alphaIA1bi;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=LiD1;
DE AltName: Full=LiP1;
DE Short=P1 {ECO:0000303|PubMed:15234562, ECO:0000303|PubMed:9790962};
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 AltName: Full=recLiD1 {ECO:0000303|PubMed:16934304};
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 NUCLEOTIDE SEQUENCE [MRNA] OF 5-306.
RC TISSUE=Venom gland;
RX PubMed=12457881; DOI=10.1016/s0041-0101(02)00201-5;
RA Kalapothakis E., Araujo S.C., de Castro C.S., Mendes T.M., Gomez M.V.,
RA Mangili O.C., Gubert I.C., Chavez-Olortegui C.;
RT "Molecular cloning, expression and immunological properties of LiD1, a
RT protein from the dermonecrotic family of Loxosceles intermedia spider
RT venom.";
RL Toxicon 40:1691-1699(2002).
RN [3]
RP PROTEIN SEQUENCE OF 27-64, 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).
RN [4]
RP IMMUNIZATION WITH RECOMBINANT PROTEIN.
RX PubMed=12565747; DOI=10.1016/s0041-0101(02)00282-9;
RA Araujo S.C., Castanheira P., Alvarenga L.M., Mangili O.C., Kalapothakis E.,
RA Chavez-Olortegui C.;
RT "Protection against dermonecrotic and lethal activities of Loxosceles
RT intermedia spider venom by immunization with a fused recombinant protein.";
RL Toxicon 41:261-267(2003).
RN [5]
RP FUNCTION.
RX PubMed=15816830; DOI=10.1111/j.0022-202x.2005.23654.x;
RA Tambourgi D.V., Paixao-Cavalcante D., Goncalves-de-Andrade R.M.,
RA Fernandes-Pedrosa M.F., Magnoli F.C., Morgan B.P., van den Berg C.W.;
RT "Loxosceles sphingomyelinase induces complement-dependent dermonecrosis,
RT neutrophil infiltration, and endogenous gelatinase expression.";
RL J. Invest. Dermatol. 124:725-731(2005).
RN [6]
RP FUNCTION.
RX PubMed=16934304; DOI=10.1016/j.toxicon.2006.06.019;
RA Felicori L., Araujo S.C., de Avila R.A., Sanchez E.F., Granier C.,
RA Kalapothakis E., Chavez-Olortegui C.;
RT "Functional characterization and epitope analysis of a recombinant
RT dermonecrotic protein from Loxosceles intermedia spider.";
RL Toxicon 48:509-519(2006).
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, PubMed:16934304).
CC The level of enzymatic activity is high according to Tambourgi and
CC colleagues or low according to Felicori and colleagues
CC (PubMed:15234562, PubMed:16934304). 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). It induces complement-dependent
CC hemolysis, dermonecrosis, vascular permeability and platelet
CC aggregation (PubMed:15234562, PubMed:9790962, PubMed:16934304). Both
CC C5a and the membrane attack complex may play a role in the induction of
CC dermonecrosis. MMP-9 and MMP-2 produced by skin fibroblasts can also
CC contribute to proteolytic tissue destruction.
CC {ECO:0000250|UniProtKB:A0A0D4WTV1, ECO:0000250|UniProtKB:P0CE80,
CC ECO:0000269|PubMed:15816830, ECO:0000269|PubMed:16934304,
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=AAP97091.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY304471; AAP97091.2; ALT_INIT; mRNA.
DR EMBL; AY340702; AAQ16123.1; -; mRNA.
DR AlphaFoldDB; P0CE81; -.
DR SMR; P0CE81; -.
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 Hemolysis; Lipid degradation; Lipid metabolism; Lyase; Magnesium;
KW Metal-binding; Secreted; Signal; Toxin; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..26
FT /evidence="ECO:0000250"
FT /id="PRO_0000392739"
FT CHAIN 27..306
FT /note="Dermonecrotic toxin LiSicTox-alphaIA1bi"
FT /id="PRO_0000392740"
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 DISULFID 78..84
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT DISULFID 80..223
FT /evidence="ECO:0000250|UniProtKB:P0CE80"
FT CONFLICT 5..7
FT /note="IVL -> ARV (in Ref. 2; AAQ16123)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="E -> EI (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="S -> F (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="E -> D (in Ref. 2; AAQ16123)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="G -> S (in Ref. 2; AAQ16123)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 306 AA; 34158 MW; A7D219AE5D9FACAE CRC64;
MLPYIVLVLG CWSVLSQAAQ TDDEERAGNR RPIWIMGHMV NAIGQIDEFV NLGANSIETD
VSFDDNANPE YTYHGIPCDC GRNCKKYENF NDFLKGLRSA TTPGNSKYQE KLVLVVFDLK
TGSLYDNQAN DAGKKLAKNL LQHYWNNGNN GGRAYIVLSI PDLNHYPLIK GFKDQLTKDG
HPELMEKVGH DFSGNDDIGD VGKAYKKAGI TGHIWQSDGI TNCLPRGLSR VNAAVANRDS
ANGFINKVYY WTVDKRSTTR DALDAGVDGI MTNYPDVITD VLNEAAYKKK FRVATYDDNP
WVTFKK
