DTPLD_HEMLE
ID DTPLD_HEMLE Reviewed; 324 AA.
AC A0A1L4BJ98;
DT 22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Dermonecrotic toxin Hl-PLD1 {ECO:0000303|PubMed:28335389};
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;
OS Hemiscorpius lepturus (Scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Scorpionoidea; Hemiscorpiidae.
OX NCBI_TaxID=520031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=27914888; DOI=10.1016/j.toxicon.2016.11.261;
RA Kazemi-Lomedasht F., Khalaj V., Bagheri K.P., Behdani M., Shahbazzadeh D.;
RT "The first report on transcriptome analysis of the venom gland of Iranian
RT scorpion, Hemiscorpius lepturus.";
RL Toxicon 125:123-130(2016).
RN [2]
RP ERRATUM OF PUBMED:27914888.
RX PubMed=28192687; DOI=10.1016/j.toxicon.2017.01.012;
RA Torabi E., Asgari S., Khalaj V., Behdani M., Kazemi-Lomedasht F.,
RA Bagheri K.P., Shahbazzadeh D.;
RT "Corrigendum to 'The first report on transcriptome analysis of the venom
RT gland of Iranian scorpion, Hemiscorpius lepturus' [Toxicon 125 (2017) 123-
RT 130].";
RL Toxicon 128:60-60(2017).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOASSAY, TOXIC DOSE, CATALYTIC
RP ACTIVITY, COFACTOR, AND 3D-STRUCTURE MODELING.
RX PubMed=28335389; DOI=10.3390/toxins9030102;
RA Torabi E., Behdani M., Chafi M.H., Moazzami R., Sabatier J.M., Khalaj V.,
RA Shahbazzadeh D., Bagheri K.P.;
RT "Characteristics and lethality of a novel recombinant dermonecrotic venom
RT phospholipase D from Hemiscorpius lepturus.";
RL Toxins 9:102-118(2017).
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) with a high activity (PubMed:28335389). It may also
CC act on ceramide phosphoethanolamine (CPE), lysophosphatidylcholine
CC (LPC) 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). In vivo,
CC shows dermonecrotic activity when intradermally injected into rabbit
CC skin and is lethal to mice (PubMed:28335389). Induces increased
CC vascular permeability, edema, inflammatory response, and platelet
CC aggregation (By similarity). Does not show hemolytic activity (at up to
CC 50 ug) (PubMed:28335389). {ECO:0000250|UniProtKB:A0A0D4WTV1,
CC ECO:0000269|PubMed:28335389}.
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:28335389};
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:0000305|PubMed:28335389};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q8I914};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:28335389}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:28335389}.
CC -!- TOXIC DOSE: LD(50) is 3.1 ug/mouse and LD(100) is 3.7 ug/mouse by
CC intraperitoneal injection into mice. {ECO:0000269|PubMed:28335389}.
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; KX932445; API81378.1; -; mRNA.
DR EMBL; KY287766; AQZ26451.1; -; Other_DNA.
DR AlphaFoldDB; A0A1L4BJ98; -.
DR SMR; A0A1L4BJ98; -.
DR BRENDA; 3.1.4.41; 13861.
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; Disulfide bond; Hemolysis;
KW Lipid degradation; Lipid metabolism; Lyase; Magnesium; Metal-binding;
KW Secreted; Signal; Toxin; Zymogen.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..324
FT /note="Dermonecrotic toxin Hl-PLD1"
FT /evidence="ECO:0000305|PubMed:27914888,
FT ECO:0000305|PubMed:28335389"
FT /id="PRO_0000442296"
FT ACT_SITE 50
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT ACT_SITE 86
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 70
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 72
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT BINDING 130
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT DISULFID 90..96
FT /evidence="ECO:0000250|UniProtKB:Q8I914"
FT DISULFID 92..236
FT /evidence="ECO:0000305"
SQ SEQUENCE 324 AA; 36979 MW; 57208E0B8645B074 CRC64;
MAHCYYNSKR GCNRVMKTVA LVVLISTVMV EESRGDSQED KKRPIWNIGH MVNAVKQIEE
FLDLGANALE ADVTFDDNGN PKWTYHGTPC DCFRDCLRWE YVDEYLKRIR ELTSPGSSKF
RKGFILLMLD LKISKLSDNA KSKAGKEIAD MIIKRLWSGS GEKAQLYIVL SFPYVNDIEF
VRAFRERVKS KGFASEAEKR IGWDISGNED LGKIRDAYQK LGITDNVWQS DGITNCLTRS
HDRLAEAVCK RDSDKEWPSL KKVYYWTVDK QSSMKEALKV GVDGMITNDP DDLVAVLNEF
SGTHRLANIN DSPWQKIPRP KSNC
