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UniProtKB - P86408 (SCXN1_MESEU)

Entry version 30 (25 May 2022)
Sequence version 2 (03 Jul 2019)
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Protein

Sodium channel neurotoxin MeuNaTxalpha-1

Gene
N/A
Organism
Mesobuthus eupeus (Lesser Asian scorpion) (Buthus eupeus)
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

Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin inhibits inactivation of Nav1.6/SCN8A (EC(50)=3.1 µM) and drosophila DmNav1 (EC(50)=1.17 µM) (PubMed:21969612, Ref. 2, PubMed:33051988).

It also shows a weak inhibition of inactivation on Nav1.2/SCN2A Nav1.3/SCN3A, and Nav1.7/SCN9A (PubMed:21969612, PubMed:33051988).

The toxin (1 µM) does not significantly shift the midpoint of activation at the two channels, but induces a significant depolarizing shift in the V(1/2) of inactivation of the channels (PubMed:21969612).

The toxin has also been shown to dose-dependently stimulates intracellular signaling in DRG neurons through activation of two kinases (type II protein kinase A (PKA-II) and MAP kinases 1/3 (MAPK1/MAPK3)) (PubMed:33051988).

Nav1.2/SCN2A is strongly suggested to be the target channel predominantly involved in this activation (PubMed:33051988).

In vivo, the toxin induces a dose-dependent thermal hyperalgesia lasting 30-45 minutes (PubMed:33051988).

2 Publications

Miscellaneous

Shows no effect on Nav1.4/SCN4A, Nav1.5/SCN5A and Nav1.8/SCN10A (PubMed:21969612, PubMed:33051988).1 Publication

<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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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 functionIon channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin

<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:
Sodium channel neurotoxin MeuNaTxalpha-12 Publications
<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>OrganismiMesobuthus eupeus (Lesser Asian scorpion) (Buthus eupeus)
<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 identifieri34648 [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 lineageiEukaryota › Metazoa › Ecdysozoa › Arthropoda › Chelicerata › Arachnida › Scorpiones › Buthida › Buthoidea › Buthidae › Mesobuthus

<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

<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the lethal dose (LD), paralytic dose (PD), effect dose (ED) or lethal concentration (LC) of a protein toxin.<p><a href='/help/toxic_dose' target='_top'>More...</a></p>Toxic dosei

LD50 is 5.8 mg/kg by subcutaneous administration into mice.1 Publication

<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 – 193 PublicationsAdd BLAST19
<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_000040111920 – 83Sodium channel neurotoxin MeuNaTxalpha-11 PublicationAdd BLAST64

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 bondi31 ↔ 82Combined sources1 Publication
Disulfide bondi35 ↔ 551 Publication
Disulfide bondi41 ↔ 651 Publication
Disulfide bondi45 ↔ 67Combined sources1 Publication
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei83Asparagine amide2 Publications1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

C-terminal amidation does not appear to play an important role in activity, since the non-amidated recombinant toxin and the native toxin (which is amidated) show similar activities on all sodium channels tested.1 Publication

Keywords - PTMi

Amidation, Disulfide bond

<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

185
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

AlphaFold Protein Structure Database

More...AlphaFoldDBi		P86408

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

More...SMRi		P86408

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<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

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini21 – 83LCN-type CS-alpha/betaPROSITE-ProRule annotationAdd BLAST63

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni27 – 31Specificity module, loop 11 Publication5
Regioni58 – 62Specificity module, loop 21 Publication5
Regioni75 – 83Specificity module, loop 31 Publication9

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

Has the structural arrangement of an alpha-helix connected to antiparallel beta-sheets by disulfide bonds (CS-alpha/beta).Curated
A labile and variable specificity module composed of 3 loops determines the selectivity of scorpion Nav alpha-toxins. In this toxin, the specificity module consists of: an N-terminal loop following beta-1 and up to the first cysteine residue (residues 27-31), the tip of the beta-2-beta-3 hairpin (58-62), and a C-terminal region (75-83).1 Publication

<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

Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Alpha subfamily.Curated

Keywords - Domaini

Signal

Family and domain databases

Conserved Domains Database

More...CDDi		cd00107, Knot1, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.30.30.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR044062, LCN-type_CS_alpha_beta_dom
IPR003614, Scorpion_toxin-like
IPR036574, Scorpion_toxin-like_sf
IPR018218, Scorpion_toxinL
IPR002061, Scorpion_toxinL/defensin

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00537, Toxin_3, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00285, SCORPNTOXIN

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00505, Knot1, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF57095, SSF57095, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51863, LCN_CSAB, 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.

P86408-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNSLVMISLA LLVMTGVESV RDGYIADDKN CAYFCGRNAY CDEECKKKGA 
        60         70         80 
ESGYCQWAGQ YGNACWCYKL PDKVPIKVSG KCNGR
Length:85
Mass (Da):9,390
Last modified:July 3, 2019 - v2
<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:i3A2504D5D2733EBA
GO

<p>This subsection of the 'Sequence' section reports information derived from mass spectrometry experiments done on the entire protein or on biologically active derived peptide(s).<p><a href='/help/mass_spectrometry' target='_top'>More...</a></p>Mass spectrometryi

Molecular mass is 7181 Da. Determined by MALDI. 1 Publication
Molecular mass is 7178.27 Da. Determined by MALDI. 1 Publication

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
EF445066 Genomic DNA Translation: ABR21041.1
HM989910 mRNA Translation: ADT82850.1

<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
EF445066 Genomic DNA Translation: ABR21041.1
HM989910 mRNA Translation: ADT82850.1

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6THINMR-A20-83[»]
AlphaFoldDBiP86408
SMRiP86408
ModBaseiSearch...
PDBe-KBiSearch...

Family and domain databases

CDDicd00107, Knot1, 1 hit
Gene3Di3.30.30.10, 1 hit
InterProiView protein in InterPro
IPR044062, LCN-type_CS_alpha_beta_dom
IPR003614, Scorpion_toxin-like
IPR036574, Scorpion_toxin-like_sf
IPR018218, Scorpion_toxinL
IPR002061, Scorpion_toxinL/defensin
PfamiView protein in Pfam
PF00537, Toxin_3, 1 hit
PRINTSiPR00285, SCORPNTOXIN
SMARTiView protein in SMART
SM00505, Knot1, 1 hit
SUPFAMiSSF57095, SSF57095, 1 hit
PROSITEiView protein in PROSITE
PS51863, LCN_CSAB, 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 nameiSCXN1_MESEU
<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: P86408
Secondary accession number(s): E4VP24, E7CZY7
<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: November 30, 2010
Last sequence update: July 3, 2019
Last modified: May 25, 2022
This is version 30 of the entry and version 2 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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