DTSPH_IXOSC
ID DTSPH_IXOSC Reviewed; 364 AA.
AC Q202J4;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2006, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Dermonecrotic toxin SPH {ECO:0000312|EMBL:ABD73957.1};
DE EC=4.6.1.- {ECO:0000250|UniProtKB:Q4ZFU2};
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;
GN Name=SPH;
OS Ixodes scapularis (Black-legged tick) (Deer tick).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; Acari;
OC Parasitiformes; Ixodida; Ixodoidea; Ixodidae; Ixodinae; Ixodes.
OX NCBI_TaxID=6945;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Salivary gland;
RA Alarcon-Chaidez F.J., Lambson B., Wikel S.K.;
RT "Functional characterization of an Ixodes scapularis (Acari: Ixodidae)
RT salivary gland protein with sphingomyelinase-like activity.";
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
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). Acts on sphingomyelin
CC (SM) (By similarity). 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 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; Evidence={ECO:0000250};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|Ref.1}.
CC -!- TISSUE SPECIFICITY: Expressed by the salivary glands.
CC {ECO:0000305|Ref.1}.
CC -!- SIMILARITY: Belongs to the arthropod phospholipase D family.
CC {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; DQ411855; ABD73957.1; -; mRNA.
DR AlphaFoldDB; Q202J4; -.
DR SMR; Q202J4; -.
DR VEuPathDB; VectorBase:ISCI021251; -.
DR VEuPathDB; VectorBase:ISCW021251; -.
DR BRENDA; 3.1.4.41; 10611.
DR Proteomes; UP000001555; Unplaced.
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; Hemolysis;
KW Lipid degradation; Lipid metabolism; Lyase; Magnesium; Metal-binding;
KW Reference proteome; Secreted; Signal; Toxin; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..364
FT /note="Dermonecrotic toxin SPH"
FT /id="PRO_0000279548"
FT ACT_SITE 29
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 65
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 49
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 51
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 109
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT DISULFID 69..75
FT /evidence="ECO:0000250"
FT DISULFID 71..215
FT /evidence="ECO:0000255"
SQ SEQUENCE 364 AA; 41567 MW; 8413E8E7571BEE0D CRC64;
MIRIFALITA LAITVKCQDD RRPFYVIGHM VNSIPQVSQF LELGTNAIES DVEFSENGTA
LRTFHGLPCD CLRRCKESAD IVDYFQYIRN VTGFRHSEYS EKLLLVFLDL KVSKLPPESK
YAAGVDIATK LVLHLWDGVP FYDAMNVLLS IGRASDMAVL TGAIDTIIGF DPSLSLFNHV
GFDVGLNDKL ENIAKMYERL GVNGHRWQGD GITNCLVNLR SPLRLKETIS YRDTNKRESY
VDKVYYWTVD KVATIRKTIR RGVDAIITNR PKRVTGVLEE DEFKKTVRPA TYRDDPWMRL
QSKTTGRGNE LDSDMDEMGD EASEFDFEPF SYPLSPRRPL SSRSPAIRDS YNVWPQYNPL
SPFY
