A1HB2_LOXIN
ID A1HB2_LOXIN Reviewed; 302 AA.
AC P0CE82; 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 40.
DE RecName: Full=Dermonecrotic toxin LiSicTox-alphaIA1bii;
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
DE AltName: Full=LiRecDT1 {ECO:0000303|PubMed:25961401};
DE AltName: Full=Loxtox i4;
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; 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).
RN [2]
RP PROTEIN SEQUENCE OF 23-60, 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 [3]
RP X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) OF 24-302 (WILD-TYPE AND H34A
RP MUTANT) IN COMPLEX WITH MAGNESIUM, METAL-BINDING SITES, COFACTOR, DISULFIDE
RP BOND, AND 3D-STRUCTURE MODELING OF MUTANTS H34A; H70A; K116A AND Y245A.
RX PubMed=25961401; DOI=10.2174/1389203716666150505231625;
RA Coronado M.A., Ullah A., da Silva L.S., Chaves-Moreira D., Vuitika L.,
RA Chaim O.M., Veiga S.S., Chahine J., Murakami M.T., Arni R.K.;
RT "Structural insights into substrate binding of brown spider venom class II
RT phospholipases D.";
RL Curr. Protein Pept. Sci. 16:768-774(2015).
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:9790962). 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 hemolysis, dermonecrosis,
CC vascular permeability and platelet aggregation (PubMed:9790962).
CC {ECO:0000250|UniProtKB:A0A0D4WTV1, 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:0000269|PubMed:25961401, ECO:0000312|PDB:4RW3,
CC ECO:0000312|PDB:4RW5};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:25961401,
CC ECO:0000312|PDB:4RW3, ECO:0000312|PDB:4RW5};
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}.
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DR EMBL; EF535253; ABU43332.1; -; mRNA.
DR PDB; 4RW3; X-ray; 1.72 A; A=24-302.
DR PDB; 4RW5; X-ray; 1.64 A; A=24-302.
DR PDBsum; 4RW3; -.
DR PDBsum; 4RW5; -.
DR AlphaFoldDB; P0CE82; -.
DR SMR; P0CE82; -.
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 3D-structure; Cytolysis; Dermonecrotic toxin; Direct protein sequencing;
KW Disulfide bond; Hemolysis; Lipid degradation; Lipid metabolism; Lyase;
KW Magnesium; Metal-binding; Secreted; Signal; Toxin; Zymogen.
FT SIGNAL <1..14
FT /evidence="ECO:0000255"
FT PROPEP 15..22
FT /evidence="ECO:0000269|PubMed:9790962"
FT /id="PRO_0000392741"
FT CHAIN 23..302
FT /note="Dermonecrotic toxin LiSicTox-alphaIA1bii"
FT /evidence="ECO:0000305|PubMed:9790962"
FT /id="PRO_0000392742"
FT ACT_SITE 34
FT /evidence="ECO:0000269|PubMed:25961401"
FT ACT_SITE 70
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:25961401"
FT BINDING 54
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:25961401,
FT ECO:0000312|PDB:4RW3, ECO:0000312|PDB:4RW5"
FT BINDING 56
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:25961401,
FT ECO:0000312|PDB:4RW3, ECO:0000312|PDB:4RW5"
FT BINDING 114
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:25961401,
FT ECO:0000312|PDB:4RW3, ECO:0000312|PDB:4RW5"
FT DISULFID 74..80
FT /evidence="ECO:0000269|PubMed:25961401,
FT ECO:0000312|PDB:4RW3, ECO:0000312|PDB:4RW5"
FT DISULFID 76..219
FT /evidence="ECO:0000269|PubMed:25961401,
FT ECO:0000312|PDB:4RW3, ECO:0000312|PDB:4RW5"
FT CONFLICT 54
FT /note="E -> EI (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="S -> F (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT NON_TER 1
FT STRAND 27..34
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 39..47
FT /evidence="ECO:0007829|PDB:4RW5"
FT STRAND 51..59
FT /evidence="ECO:0007829|PDB:4RW5"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 86..96
FT /evidence="ECO:0007829|PDB:4RW5"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 125..139
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:4RW5"
FT STRAND 151..157
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 159..162
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 163..174
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 178..183
FT /evidence="ECO:0007829|PDB:4RW5"
FT STRAND 184..188
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 194..204
FT /evidence="ECO:0007829|PDB:4RW5"
FT STRAND 208..215
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 225..234
FT /evidence="ECO:0007829|PDB:4RW5"
FT STRAND 243..247
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 252..260
FT /evidence="ECO:0007829|PDB:4RW5"
FT STRAND 264..269
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 271..278
FT /evidence="ECO:0007829|PDB:4RW5"
FT HELIX 281..284
FT /evidence="ECO:0007829|PDB:4RW5"
FT STRAND 287..289
FT /evidence="ECO:0007829|PDB:4RW5"
SQ SEQUENCE 302 AA; 33641 MW; 0E97975AA4424F72 CRC64;
ARVVLGCWSV LSQAAQTDDE ERAGNRRPIW IMGHMVNAIG QIDEFVNLGA NSIETDVSFD
DNANPEYTYH GIPCDCGRNC KKYENFNDFL KGLRSATTPG NSKYQEKLVL VVFDLKTGSL
YDNQANDAGK KLAKNLLQHY WNNGNNGGRA YIVLSIPDLN HYPLIKGFKD QLTKDGHPEL
MDKVGHDFSG NDDIGDVGKA YKKAGITGHI WQSDGITNCL PRGLSRVNAA VANRDSANGF
INKVYYWTVD KRSTTRDALD AGVDGIMTNY PDVITDVLNE AAYKKKFRVA TYDDNPWVTF
KK
