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UniProtKB - P59867 (KAX63_HETSP)

Entry version 84 (25 May 2022)
Sequence version 1 (26 Sep 2003)
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Protein

Potassium channel toxin alpha-KTx 6.3

Gene
N/A
Organism
Heterometrus spinifer (Asia giant forest scorpion) (Malaysian black scorpion)
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

Potently blocks voltage-gated potassium channels Kv1.1/KCNA1 (IC50=7-11 nM) and Kv1.3/KCNA3 (IC50=11-29 pM) (PubMed:9359871, PubMed:24676092, PubMed:15498765).

Also mildly blocks intermediate (IK) conductance calcium-activated potassium channels (KCa3.1/KCNN4) and ERG1/Kv11.1/KCNH2 (PubMed:18687312, PubMed:15498765).

Shows ability to suppress proliferation of lymphocytes, which are known to be sensitive to Kv1.3/KCNA3 homotetrameric channel block (PubMed:24676092).

4 Publications

Miscellaneous

Does not block Kv1.2/KCNA2 potassium channels (PubMed:15498765). Does not induce hemolysis (PubMed:24676092).2 Publications
PEGylation of HsTX1[R14A] enhances its circulating half-life in rats, reduces its affinity but not its selectivity for Kv1.3/KCNA3, and dramatically reduces its adsorption to inert surfaces. PEG-HsTX1[R14A] is equipotent to HsTX1[R14A] in preferential inhibition of human and rat CCR7- effector memory T lymphocytes (TEM) proliferation, leaving CCR7+ naive and central memory T cells able to proliferate. It reduces inflammation in an active delayed-type hypersensitivity model and in the pristane-induced arthritis (PIA) model of rheumatoid arthritis (RA). Importantly, a single subcutaneous dose of PEG-HsTX1[R14A] reduces inflammation in PIA for a longer period of time than the non-PEGylated HsTX1[R14A]. Together, these data indicate that HsTX1[R14A] and PEG-HsTX1[R14A] are effective in a model of RA and are therefore potential therapeutics for TEM cell-mediated autoimmune diseases.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei21Important for activity1 Publication1
Sitei23Critical for activity (is inserted in the pore, pointing downward)1 Publication1
Sitei25Important for activity1 Publication1
Sitei26Important for activity1 Publication1
Sitei33Important for activity1 Publication1

<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 ...

<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-activated potassium channel impairing toxin, Ion channel impairing toxin, Neurotoxin, Potassium channel impairing toxin, Toxin, Voltage-gated potassium 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:
Potassium channel toxin alpha-KTx 6.3
Alternative name(s):
Neurotoxin HsTX11 Publication
<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>OrganismiHeterometrus spinifer (Asia giant forest scorpion) (Malaysian black scorpion)
<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 identifieri118530 [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 › Iurida › Scorpionoidea › Scorpionidae › Heterometrinae › Heterometrus

<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 '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

Some analogs of this peptide are potential candidate for treatment of autoimmune diseases through block of Kv1.3/KCNA3.2 Publications

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>Mutagenesisi14R → A: Increase in selectivity for Kv1.3/KCNA3 over Kv1.1/KCNA1 (>2000-fold more selective). Very weak decrease in inhibition of Kv1.3/KCNA3 and important decrease in inhibition of Kv1.1/KCNA1. No change in ability to suppress lymphocyte proliferation. 2 Publications1

<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_00000449081 – 34Potassium channel toxin alpha-KTx 6.31 PublicationAdd BLAST34

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 bondi3 ↔ 24Combined sources3 PublicationsImported
Disulfide bondi9 ↔ 29Combined sources3 PublicationsImported
Disulfide bondi13 ↔ 31Combined sources3 PublicationsImported
Disulfide bondi19 ↔ 34Combined sources3 Publications
<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 residuei34Cysteine amide1 Publication1

<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

Amidated (PubMed:9359871). The amidated toxin shows 5-fold more affinity for Kv1.3/KCNA3 than the synthetic carboxylated form (PubMed:9359871).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

134
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

AlphaFold Protein Structure Database

More...AlphaFoldDBi		P59867

Biological Magnetic Resonance Data Bank

More...BMRBi		P59867

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

More...SMRi		P59867

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P59867

<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

Has the structural arrangement of an alpha-helix connected to a beta-sheet by disulfide bonds (CSalpha/beta).2 Publications
The lower affinity for Kv1.1/KCNA1 is due to HsTX1 inability to come close to the pore domain, which prevents the pore-inserting lysine (Lys-23) from making proper contacts with the tyrosine carbonyls in the selectivity filter of the channel.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 short scorpion toxin superfamily. Potassium channel inhibitor family. Alpha-KTx 06 subfamily.Curated

Family and domain databases

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
IPR036574, Scorpion_toxin-like_sf
IPR001947, Scorpion_toxinS_K_inh

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00451, Toxin_2, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00286, CHARYBDTOXIN

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
PS01138, SCORP_SHORT_TOXIN, 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.

P59867-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30 
ASCRTPKDCA DPCRKETGCP YGKCMNRKCK CNRC
Length:34
Mass (Da):3,828
Last modified:September 26, 2003 - 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:i6078F957A4FDF39A
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 3815.63 Da. 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:

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
1QUZNMR-A1-34[»]
1WPDNMR-A7-34[»]
1Y2PNMR-A1-34[»]
AlphaFoldDBiP59867
BMRBiP59867
SMRiP59867
ModBaseiSearch...
PDBe-KBiSearch...

Miscellaneous databases

EvolutionaryTraceiP59867

Family and domain databases

Gene3Di3.30.30.10, 1 hit
InterProiView protein in InterPro
IPR036574, Scorpion_toxin-like_sf
IPR001947, Scorpion_toxinS_K_inh
PfamiView protein in Pfam
PF00451, Toxin_2, 1 hit
PRINTSiPR00286, CHARYBDTOXIN
SUPFAMiSSF57095, SSF57095, 1 hit
PROSITEiView protein in PROSITE
PS01138, SCORP_SHORT_TOXIN, 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 nameiKAX63_HETSP
<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: P59867
<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: September 26, 2003
Last sequence update: September 26, 2003
Last modified: May 25, 2022
This is version 84 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. Scorpion potassium channel toxins
    Nomenclature of scorpion potassium channel toxins and list of entries
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
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