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Stichodactyla helianthus (Sun anemone) (Stoichactis helianthus)
Reviewed-Annotation score: -Experimental evidence at protein leveli


Inhibits voltage-dependent potassium channels. Potently blocks Kv1.1/KCNA1 (IC50=6.7-87 pM) and Kv1.3/KCNA3 (IC50=10-250 pM) (PubMed:8567178, PubMed:15665253, PubMed:9830012, PubMed:10545177, PubMed:23919482, PubMed:26288216, PubMed:28194851). Less potently blocks Kv1.4/KCNA4 (IC50=0.31 nM), and Kv1.6/KCNA6 (IC50=0.16 nM) (PubMed:9830012). Shows moderate activity on Kv1.2/KCNA2 (IC50=9 nM), Kv1.7/KCNA7 (IC50=11.5 nM), and KCa3.1/KCNN4 (Kd=0.03-30 nM) (PubMed:10419508, PubMed:9830012). Blocks Kv channels by binding to a shallow vestibule at the outer entrance to the ion conduction pathway and occluding the entrance to the pore (PubMed:10419508, PubMed:9830012).9 Publications


Does not show or very weak activity on Kv1.5/KCNA5, Kv3.1/KCNC1, and Kv3.4/KCNC4 (IC50>100 nM).1 Publication
The synthetic analog ShK-192 has a paraphosphono-Phe (Ppa) at position 0, a Norleucine at position 21, and is amidated. It is stable at acidic pH values and high temperatures. The circulating half-life of the synthetic mutant is estimated to be about 30 minutes in rats. However, low concentrations of functionally active peptide are detected in the blood 72 hours after the injection. The synthetic mutant effectively inhibits the proliferation of T lymphocytes (T(EM)) cells in rats and suppresses delayed type hypersensitivity when administered at 10 or 100 µg/kg by subcutaneous injection once daily.1 Publication
The synthetic analog ShK-145 has a 20 kDa polyethylene glycol (PEG), and a Lys at position 16. In vivo, its injection into rat model of multiple sclerosis inhibits the progression of the disease. In addition, weekly administration of ShK-145 suppress interleukin-17 (IL-17) cytokine secretion from T cells in cynomolgus monkeys and does not show adverse side effects.1 Publication
The synthetic analog ShK-L5 contains a L-phosphotyrosine linked via a hydrophilic linker to the N-terminus of the ShK peptide. It is a highly specific Kv1.3/KCNA3 blocker that exhibits 100-fold selectivity for Kv1.3/KCNA3 over Kv1.1/KCNA1 and greater than 250-fold selectivity over all other channels tested. In vivo, it does not cause cardiac toxicity and does not alter clinical chemistry and hematological parameters after 2-week therapy. It also prevents and treats experimental autoimmune encephalomyelitis and suppresses delayed type hypersensitivity in rats.1 Publication


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei7Important residue for binding Kv1.3/KCNA31 Publication1
Sitei9Important residue for binding Kv1.3/KCNA31 Publication1
Sitei11Important residue for binding Kv1.3/KCNA32 Publications1
Sitei20Important residue for binding Kv1.3/KCNA31 Publication1
Sitei21Important residue for binding Kv1.3/KCNA31 Publication1
Sitei22Key residue for binding both Kv1.2/KCNA2 and Kv1.3/KCNA3 (occludes the channel pore like a cork in a bottle)2 Publications1
Sitei23Important residue for binding Kv1.3/KCNA31 Publication1
Sitei27Important residue for binding Kv1.3/KCNA31 Publication1

GO - Molecular functioni


Molecular functionIon channel impairing toxin, Neurotoxin, Potassium channel impairing toxin, Toxin, Voltage-gated potassium channel impairing toxin

Protein family/group databases

TCDBi8.B.14.1.2 the sea anemone peptide toxin, class 1 (bgk) family

Names & Taxonomyi

Protein namesi
Recommended name:
Kappa-stichotoxin-She3a1 Publication
Short name:
Kappa-SHTX-She3a1 Publication
Alternative name(s):
Potassium channel toxin ShK1 Publication
OrganismiStichodactyla helianthus (Sun anemone) (Stoichactis helianthus)
Taxonomic identifieri6123 [NCBI]
Taxonomic lineageiEukaryotaMetazoaCnidariaAnthozoaHexacoralliaActiniariaStichodactylidaeStichodactyla

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

Nematocyst, Secreted

Pathology & Biotechi

Pharmaceutical usei

Synthetic analog ShK-186 is under preclinical trial by "Kv1.3 Therapeutics, Inc." under the name dalazatide. Dalazatide has been validated in multiple models of autoimmune disease and has demonstrated proof of concept in a Phase 1b study in psoriasis. Dalazatide is ready to begin Phase 2 clinical studies for inclusion body myositis (IBM) a rare disease with no approved treatment options and generally poor prognosis for the patients. The dalazatide development program is focused on providing a breakthrough treatment first for IBM and then followed by other rare and autoimmune diseases. ShK-186 contains an L-phosphotyrosine attached via an aeea (mini-PEG) hydrophilic linker to Arg-1 and is amidated.2 Publications


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi7I → Q: 10-fold decrease in potency of inhibition of Kv1.3/KCNA3. 1 Publication1
Mutagenesisi9K → Q: 10-fold decrease in potency of inhibition of Kv1.3/KCNA3. 1 Publication1
Mutagenesisi11R → Q: 7.5- to 42-fold decrease in potency of inhibition of Kv1.3/KCNA3. 2 Publications1
Mutagenesisi16Q → K: 6.6-fold increase in selectivity for Kv1.3/KCNA3 over Kv1.1/KCNA1, which is marked by a 2.6-fold and 117-fold decrease in potency of inhibition of Kv1.3/KCNA3 and Kv1.1/KCNA1, respectively. 1 Publication1
Mutagenesisi20S → A: 20-fold decrease in potency of inhibition of Kv1.3/KCNA3, and 80-fold decrease in potency of inhibition of KCa3.1/KCNN4. 1 Publication1
Mutagenesisi20S → Q or R: More than 25-fold decrease in potency of inhibition of Kv1.3/KCNA3. 1 Publication1
Mutagenesisi21M → Q: More than 25-fold decrease in potency of inhibition of Kv1.3/KCNA3. 1 Publication1
Mutagenesisi22K → Q or R: More than 25-fold decrease in potency of inhibition of Kv1.3/KCNA3. 2 Publications1
Mutagenesisi23Y → Q or R: More than 25-fold decrease in potency of inhibition of Kv1.3/KCNA3. 1 Publication1
Mutagenesisi27F → Q or R: More than 25-fold decrease in potency of inhibition of Kv1.3/KCNA3. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PeptideiPRO_00000448661 – 35Kappa-stichotoxin-She3a2 PublicationsAdd BLAST35

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi3 ↔ 354 PublicationsImported
Disulfide bondi12 ↔ 285 PublicationsImported
Disulfide bondi17 ↔ 325 PublicationsImported

Keywords - PTMi

Disulfide bond


Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 7Combined sources5
Helixi9 – 11Combined sources3
Helixi14 – 17Combined sources4
Helixi21 – 25Combined sources5
Turni29 – 33Combined sources5

3D structure databases

Select the link destinations:
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum

Miscellaneous databases


Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 35ShKTPROSITE-ProRule annotationAdd BLAST33

Sequence similaritiesi

Family and domain databases

InterProiView protein in InterPro
IPR003582 ShKT_dom
PROSITEiView protein in PROSITE
PS51670 SHKT, 1 hit


Sequence statusi: Complete.

P29187-1 [UniParc]FASTAAdd to basket

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        10         20         30 
Mass (Da):4,061
Last modified:December 1, 1992 - v1

Mass spectrometryi

Molecular mass is 4054.82±0.1 Da from positions 1 - 35. Determined by ESI. 1 Publication

Similar proteinsi

Entry informationi

Entry nameiK1A_STIHL
AccessioniPrimary (citable) accession number: P29187
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: April 25, 2018
This is version 105 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program


Keywords - Technical termi

3D-structure, Direct protein sequencing, Pharmaceutical
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Main funding by: National Institutes of Health