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Entry version 44 (02 Jun 2021)
Sequence version 1 (23 Mar 2010)
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Protein

Dermonecrotic toxin LiSicTox-alphaIA1a

Gene
N/A
Organism
Loxosceles intermedia (Brown spider)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Dermonecrotic toxins cleave the phosphodiester linkage between the phosphate and headgroup of certain phospholipids (sphingolipid and lysolipid substrates), forming an alcohol (often choline) and a cyclic phosphate (By similarity).

This toxin acts on sphingomyelin (SM) with high activity (PubMed:16581177, PubMed:9790962, PubMed:21590705, PubMed:27233517).

It also acts on lysophosphatidylcholine (LPC), and lyso-platelet activating factor (LPAF, an alkyl-LPC) but not on phosphatidylcholine (PC) (PubMed:21590705, PubMed:27233517).

It may also act on ceramide phosphoethanolamine (CPE), lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), but not on lysophosphatidylserine (LPS), and lysophosphatidylglycerol (LPG) (By similarity).

It acts by transphosphatidylation, releasing exclusively cyclic phosphate products as second products (By similarity).

In vivo, it induces dermonecrosis, vascular permeability, platelet aggregation, inflammatory response, edema and cytotoxicity against renal epithelial cells (PubMed:16581177, PubMed:9790962, PubMed:17900646, PubMed:27233517).

It causes direct nephrotoxicity (PubMed:16005484) and is directly toxic to liver (PubMed:18765244).

It also induces hemolysis in a complement-dependent manner as well as in a complement-independent manner (PubMed:9790962, PubMed:17900646, PubMed:21590705, PubMed:27233517).

The hemolysis provoked in a complement-independent manner is composed of several steps (PubMed:21590705).

The toxin binds to erythrocyte membranes, hydrolyzes membrane phospholipids (SM and LPC) thus generating metabolism products that cause hemolysis, probably by provoking an increase of calcium inside cells (PubMed:21590705).

The calcium influx is due to the opening of L-type calcium channels, since L-type calcium channel blockers inhibit calcium influx (PubMed:21590705).

In vivo, is lethal to mice when intraperitoneally injected (PubMed:17900646).

By similarity7 Publications

Caution

The most common activity assay for dermonecrotic toxins detects enzymatic activity by monitoring choline release from substrate. Liberation of choline from sphingomyelin (SM) or lysophosphatidylcholine (LPC) is commonly assumed to result from substrate hydrolysis, giving either ceramide-1-phosphate (C1P) or lysophosphatidic acid (LPA), respectively, as a second product. However, two studies from Lajoie and colleagues (2013 and 2015) report the observation of exclusive formation of cyclic phosphate products as second products, resulting from intramolecular transphosphatidylation. Cyclic phosphates have vastly different biological properties from their monoester counterparts, and they may be relevant to the pathology of brown spider envenomation.By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mg2+2 PublicationsImportedNote: Binds 1 Mg2+ ion per subunit.2 PublicationsImported

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Catalytic activity and hemolysis are inhibited by divalent ion chelators (1,10-phenanthroline, EDTA, and EGTA).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei385 Publications1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi58Magnesium2 PublicationsImported1
Metal bindingi60Magnesium2 PublicationsImported1
Active sitei74Nucleophile1 Publication1
Metal bindingi118Magnesium2 PublicationsImported1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDermonecrotic toxin, Lyase, Toxin
Biological processCytolysis, Hemolysis, Lipid degradation, Lipid metabolism
LigandMagnesium, Metal-binding

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Dermonecrotic toxin LiSicTox-alphaIA1a (EC:4.6.1.-By similarity)
Alternative name(s):
Dermonecrotic toxin 11 Publication
Short name:
DT11 Publication
Short name:
LiRecDT12 Publications
P11 Publication
Phospholipase D
Short name:
PLD
Sphingomyelin phosphodiesterase D 1
Short name:
SMD 1
Short name:
SMase D 1
Short name:
Sphingomyelinase D 1
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiLoxosceles intermedia (Brown spider)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri58218 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaAraneaeAraneomorphaeHaplogynaeScytodoideaSicariidaeLoxosceles

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi38H → A: Loss of catalytic activity on sphingomyelin and lysophosphatidylcholine, and loss of hemolytic, vascular permeability, nephrotoxic, and dermonecrotic activities. Loss of catalytic activity on sphingomyelin and lysophosphatidylcholine, and loss of hemolytic, vascular permeability, and dermonecrotic activities; when associated with A-74. 5 Publications1
Mutagenesisi58E → A: Loss of catalytic activity on sphingomyelin. Loss of catalytic activity on sphingomyelin and lysophosphatidylcholine, high decrease of hemolytic activity, and loss of vascular permeability and dermonecrotic activities; when associated with A-60. 1 Publication1
Mutagenesisi60D → A: Loss of catalytic activity on sphingomyelin. Loss of catalytic activity on sphingomyelin and lysophosphatidylcholine, high decrease of hemolytic activity, and loss of vascular permeability and dermonecrotic activities; when associated with A-58. 1 Publication1
Mutagenesisi74H → A: Loss of catalytic activity on sphingomyelin. Loss of catalytic activity on sphingomyelin and lysophosphatidylcholine, and high decrease of hemolytic activity; when associated with A-38. 1 Publication1
Mutagenesisi80C → A: Moderate decrease of catalytic activity on sphingomyelin and lysophosphatidylcholine, and moderate decrease of hemolytic, vascular permeability, and dermonecrotic activities; when associated with A-223. 1 Publication1
Mutagenesisi120K → A: Important decrease of catalytic activity on sphingomyelin and lysophosphatidylcholine, and moderate decrease of hemolytic, vascular permeability, and dermonecrotic activities. 1 Publication1
Mutagenesisi122G → A: No or very weak change in catalytic activity on sphingomyelin and lysophosphatidylcholine, and no change in hemolytic, vascular permeability, and dermonecrotic activities. 1 Publication1
Mutagenesisi223C → A: Moderate decrease of catalytic activity on sphingomyelin and lysophosphatidylcholine, and moderate decrease of hemolytic, vascular permeability, and dermonecrotic activities; when associated with A-80. 1 Publication1
Mutagenesisi249Y → A: Loss of catalytic activity on sphingomyelin and lysophosphatidylcholine, high decrease of hemolytic activity, and loss of vascular permeability and dermonecrotic activities. 1 Publication1
Mutagenesisi251W → A: Moderate decrease of catalytic activity on sphingomyelin and lysophosphatidylcholine, and moderate decrease of hemolytic, vascular permeability, and dermonecrotic activities. 1 Publication1

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 18Sequence analysisAdd BLAST18
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_000003557919 – 261 Publication8
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000003558027 – 306Dermonecrotic toxin LiSicTox-alphaIA1a1 PublicationAdd BLAST280

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi78 ↔ 842 PublicationsImported
Disulfide bondi80 ↔ 2232 PublicationsImported

Keywords - PTMi

Disulfide bond, Zymogen

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed by the venom gland.1 Publication

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1306
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P0CE80

Database of comparative protein structure models

More...
ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
P0CE80

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Signal

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
3.20.20.190, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR017946, PLC-like_Pdiesterase_TIM-brl

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF51695, SSF51695, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

P0CE80-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLPYIVLVLG CWSVLSQAAQ TDDEERAGNR RPIWIMGHMV NAIGQIDEFV
60 70 80 90 100
NLGANSIETD VSFDDNANPE YTYHGIPCDC GRNCKKYENF NDFLKGLRSA
110 120 130 140 150
TTPGNSKYQE KLVLVVFDLK TGSLYDNQAN DAGKKLAKNL LQHYWNNGNN
160 170 180 190 200
GGRAYIVLSI PDLNHYPLIK GFKDQLTKDG HPELMDKVGH DFSGNDDIGD
210 220 230 240 250
VGKAYKKAGI TGHIWQSDGI TNCLPRGLSR VNAAVANRDS ANGFINKVYY
260 270 280 290 300
WTVDKRSTTR DALDAGVDGI MTNYPDVITD VLNEAAYKKK FRVATYDENP

WVTFKK
Length:306
Mass (Da):34,158
Last modified:March 23, 2010 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iA62718AE5D9FADAE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti58E → EI AA sequence (PubMed:9790962).Curated1
Sequence conflicti62S → F AA sequence (PubMed:9790962).Curated1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
DQ218155 mRNA Translation: ABA62021.1

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ218155 mRNA Translation: ABA62021.1

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3RLGX-ray1.60A28-306[»]
3RLHX-ray1.72A1-306[»]
SMRiP0CE80
ModBaseiSearch...
PDBe-KBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0CE80

Family and domain databases

Gene3Di3.20.20.190, 1 hit
InterProiView protein in InterPro
IPR017946, PLC-like_Pdiesterase_TIM-brl
SUPFAMiSSF51695, SSF51695, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiA1HA_LOXIN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P0CE80
Secondary accession number(s): B2KKV9
, P83045, Q3HL91, Q6W8Q5, Q7YW73
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 23, 2010
Last sequence update: March 23, 2010
Last modified: June 2, 2021
This is version 44 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
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