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Entry version 50 (18 Jul 2018)
Sequence version 1 (25 Oct 2005)
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Protein

Beta-theraphotoxin-Cm1a

Gene
N/A
Organism
Ceratogyrus marshalli (Straighthorned baboon tarantula) (Ceratogyrus cornuatus)
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

Inhibits many voltage-gated sodium channels and one voltage-gated calcium channel (Cav2.2/CACNA1B (IC50=400 nM), Nav1.2/SCN2A (IC50=3-70 nM), Nav1.1/SCN1A (523-1060 nM), Nav1.7/SCN9A (5120 nM), Nav1.4/SCN4A (888 nM or >10 µM) and Nav1.5/SCN5A (323 nM or >10 µM)) (PubMed:16267209, PubMed:27129258, PubMed:28880874). It acts by shifting the voltage dependence of channel activation to more depolarized potentials and by blocking the inward component of the sodium current (PubMed:16267209). On Nav1.7/SCN9A, it has been shown to interact with the S3-S4 loop of domain DII (site 4) (PubMed:27129258). Is significantly more potent against Nav1.2/SCN2A than the other Nav channel subtypes (PubMed:16267209). In vivo, this toxin causes general ataxia, lack of response to stimuli, and semiparalysis (PubMed:16267209). After a few minutes, the mice are unable to stand, and breathing is reduced in rhythm and intensity (PubMed:16267209). Symptoms gradually increase with progressive slowing of breathing and flaccid paralysis, death occurred within 10 to 20 minutes post injection (PubMed:16267209). Animals remain totally flaccid, and no symptoms of excitatory neurotoxicity are observed (PubMed:16267209).3 Publications

Miscellaneous

Synthetic variant D1Z/M5I/K18Y/R24Ka has a N-terminal pyroglutamate and a C-terminal amidation. It shows an IC50=2.7 nM on Nav1.7/SCN9A and IC50>3 µM on Nav1.4/SCN4A and Nav1.5/SCN5A.1 Publication
Synthetic variant D1Z/M5I/R27Na has a N-terminal pyroglutamate and a C-terminal amidation. It shows an IC50=2.8 nM on Nav1.7/SCN9A and IC50>3 µM on Nav1.4/SCN4A and Nav1.5/SCN5A.1 Publication
Does not inhibit Cav1.3/CACNA1D and Cav3.1/CACNA1G (PubMed:28880874). Does not inhibit Nav1.3/SCN3A, Nav1.6/SCN8A, Nav1.8/SCN10A (PubMed:16267209, PubMed:28880874).2 Publications

<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

  • sodium channel inhibitor activity Source: UniProtKB
  • toxin activity Source: UniProtKB-KW

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 functionCalcium channel impairing toxin, Ion channel impairing toxin, Neurotoxin, Toxin, Voltage-gated calcium channel impairing 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_and_taxonomy_section">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:
Beta-theraphotoxin-Cm1aCurated
Short name:
Beta-TRTX-Cm1aCurated
Alternative name(s):
Ceratotoxin-12 Publications
Short name:
CcoTx12 Publications
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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>OrganismiCeratogyrus marshalli (Straighthorned baboon tarantula) (Ceratogyrus cornuatus)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 identifieri316287 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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 lineageiEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaAraneaeMygalomorphaeTheraphosidaeCeratogyrus

Organism-specific databases

ArachnoServer: Spider toxin database

More...
ArachnoServeri
AS000221 beta-theraphotoxin-Cm1a

<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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 ‘Pathology and Biotech’ section describes the use of a protein as a pharmaceutical drug. It indicates the name of the drug, the name of the firm that commercializes it and explains in a few words in which context the drug is used. In some cases, drugs that are under development are also described.<p><a href='/help/pharmaceutical_use' target='_top'>More...</a></p>Pharmaceutical usei

Derivatives such as D1Z/M5I/K18Y/R24Ka or D1Z/M5I/R27Na are under preclinical trial by Pfizer to treat pain.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'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>Mutagenesisi5W → I: Important increase in potency toward Nav1.7/SCN9A, and low potency on Nav1.4/SCN4A and Nav1.5/SCN5A; synthetic variant D1Z/M5I/K18Y/R24Ka and synthetic variant D1Z/M5I/R27Na. 1 Publication1
Mutagenesisi12K → E: Important increase in potency toward Nav1.7/SCN9A, and low potency on Nav1.4/SCN4A and Nav1.5/SCN5A; synthetic variant D1Z/M5I/K18Y/R24Ka and synthetic variant D1Z/M5I/R27Na. 1 Publication1
Mutagenesisi18K → Y: Important increase in potency toward Nav1.7/SCN9A, and low potency on Nav1.4/SCN4A and Nav1.5/SCN5A; synthetic variant D1Z/M5I/K18Y/R24Ka. 1 Publication1
Mutagenesisi19 – 21NYT → RLV: Important increase in potency toward Nav1.7/SCN9A, and low potency on Nav1.4/SCN4A and Nav1.5/SCN5A; synthetic variant D1Z/M5I/K18Y/R24Ka and synthetic variant D1Z/M5I/R27Na. 1 Publication3
Mutagenesisi24R → K: Important increase in potency toward Nav1.7/SCN9A, and low potency on Nav1.4/SCN4A and Nav1.5/SCN5A; synthetic variant D1Z/M5I/K18Y/R24Ka. 1 Publication1
Mutagenesisi25 – 26RD → SH: Important increase in potency toward Nav1.7/SCN9A, and low potency on Nav1.4/SCN4A and Nav1.5/SCN5A; synthetic variant D1Z/M5I/K18Y/R24Ka and synthetic variant D1Z/M5I/R27Na. 1 Publication2
Mutagenesisi27R → N: Important increase in potency toward Nav1.7/SCN9A, and low potency on Nav1.4/SCN4A and Nav1.5/SCN5A; synthetic variant D1Z/M5I/R27Na. 1 Publication1
Mutagenesisi31 – 32YD → WK: Important increase in potency toward Nav1.7/SCN9A, and low potency on Nav1.4/SCN4A and Nav1.5/SCN5A; synthetic variant D1Z/M5I/K18Y/R24Ka and synthetic variant D1Z/M5I/R27Na. 1 Publication2

<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 describes the position and length of an active peptide in the mature protein.<p><a href='/help/peptide' target='_top'>More...</a></p>PeptideiPRO_00000450001 – 33Beta-theraphotoxin-Cm1a1 PublicationAdd BLAST33

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 bondi2 ↔ 171 Publication
Disulfide bondi9 ↔ 221 Publication
Disulfide bondi16 ↔ 291 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 residuei33Leucine amide1 Publication1

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

133
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5EPMX-ray1.75C/D1-33[»]
6BR0NMR-A1-33[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P84507

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

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SMRi
P84507

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
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

<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

The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.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

Keywords - Domaini

Knottin

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR011696 Huwentoxin-1
IPR013140 Huwentoxin_CS1

Pfam protein domain database

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Pfami
View protein in Pfam
PF07740 Toxin_12, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS60021 HWTX_1, 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_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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.

P84507-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30 
DCLGWFKSCD PKNDKCCKNY TCSRRDRWCK YDL
Length:33
Mass (Da):4,052
Last modified:October 25, 2005 - 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:i2DED2300E19FFF1A
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 4041.79 Da from positions 1 - 33. Determined by MALDI. 1 Publication

<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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5EPMX-ray1.75C/D1-33[»]
6BR0NMR-A1-33[»]
ProteinModelPortaliP84507
SMRiP84507
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ArachnoServeriAS000221 beta-theraphotoxin-Cm1a

Family and domain databases

InterProiView protein in InterPro
IPR011696 Huwentoxin-1
IPR013140 Huwentoxin_CS1
PfamiView protein in Pfam
PF07740 Toxin_12, 1 hit
PROSITEiView protein in PROSITE
PS60021 HWTX_1, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
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 nameiTX1_CERMR
<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: P84507
<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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: October 25, 2005
Last modified: July 18, 2018
This is version 50 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, Pharmaceutical

Documents

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